it 
 is the active agent in front - line chemotherapeutic drugs used for 
 treatment of a variety of cancers . because it 
 is only minimally water - soluble , ptx is administered to humans as 
 a drug formulation that is formed by its solubilization with an emulsifier 
 [ a 1:1 ( v / v ) mixture of polyethoxylated castor oil and absolute ethanol ] , 
 with human serum albumin , or with peg - pla . these formulations comprise 
 a significant advance in chemotherapeutics , but the drug loading is 
 relatively low ( 1.1 , 10 , and 16.7 wt % ptx , respectively ) . in the 
 case of the first , significant undesirable side effects of the emulsifier similarly , the closely related taxane 
 docetaxel ( dtx ) is administered as an ethanolic suspension of 4% wt / vol 
 dtx in polysorbate 80 . because these taxanes are such effective 
 cytotoxins , new conceptual 
 and practical strategies for improving the administration of ptx and 
 dtx remain desirable . in particular , drug delivery vehicles containing 
 higher drug loading levels than currently in the front - line drug formulations 
 mentioned above have the potential to be quite advantageous . accordingly , 
 we envision that proper matching of the physicochemical properties 
 of a taxane derivative with a suitable polymer - based drug carrier 
 might allow for formulation of an effective nanoparticle drug delivery 
 entity . one potentially attractive strategy is the incorporation of 
 drugs into block copolymer ( bcp ) based nanoparticles ( nps ) by rapid 
 co - precipitation of the drug and the bcp in a process known as flash 
 nanoprecipitation ( fnp ) . this can provide nps 
 with dimensions attractive from a drug delivery perspective and that 
 are highly loaded ( to 50 wt % ) with the small molecule drug 
 agent . fnp has been used to prepare nps comprising ptx and various 
 bcps , in particular , the biocompatible poly(ethylene glycol)-b - poly(ester ) amphiphilic block polymer peg - pcl , peg - pla , 
 or peg - plga [ where the poly(ester ) is poly(caprolactone ) , poly(lactic 
 acid ) , or poly(lactic / glycolic acid ) , respectively ] . however , the resulting aqueous dispersions of these ptx - loaded nps 
 were kinetically unstable ; the ptx exited the hydrophobic core of 
 the particle and crystallized in the exterior in a matter of minutes , 
 presumably via the mechanism of ostwald ripening . we 
 envision that this undesirable process could be arrested by use of 
 a modified taxane derivative that is more hydrophobic 
 than the parent drug molecule . moreover , if that derivative is susceptible 
 to reversion back to the parent taxane , say by simple hydrolysis , 
 then it could serve as a taxane prodrug . we hypothesized that 
 silicate esters , tetraalkoxysilanes [ ( ro)4si ] , comprise 
 a class of derivatives that meet these requirements . a parent 
 drug molecule containing a reactive hydroxyl group is converted to 
 its tetraalkoxysilane ( the silicate derivative ) by reaction with a 
 trialkoxychlorosilane derivatizing agent . note that a number of studies imply that orthosilicic acid [ si(oh)4 ] , the ultimate stoichiometric byproduct of silicate ester 
 cleavage , does not pose any significant toxicity issues . the nature of the three auxiliary r groups in the silicate prodrug 
 ( figure 1 ) would provide considerable flexibility 
 in allowing for adjustment of the degree of hydrophobicity as well 
 as the hydrolytic stability of the derivative . desimone and co - workers 
 recently described a construct that capitalized on the second of these 
 features : alteration of steric hindrance at silicon to impact hydrolysis 
 and drug release . they used nanoparticles 
 derived from nanoparticle - bound dialkoxydialkylsilanes ( or silaketals ) 
 having the formulation of polyacrylate osi(r2)o  drug 
 ( where drug is camptothecin , dasatinib , or gemcitabine ) and demonstrated 
 that the steric bulk of the alkyl groups ( r = ethyl , isopropyl , or tert - butyl ) altered the hydrolysis rate , thereby allowing 
 for controlled release rates of the drug from its carrier . modification of a hydroxyl 
 group in the drug with a trialkoxychlorosilane generates the ( labile ) 
 silicate derivative , which following administration undergoes hydrolysis 
 to return the free drug along with benign alcohol and orthosilicic 
 acid byproducts . numerous prodrugs and 
 derivatives of ptx and dtx have been explored , 
 in part with an eye toward identification of a bioactive agent that 
 might no longer require the use of any formulation agent . the vast majority of these efforts have centered 
 on increasing the hydrophilicity of the parent taxane 
 with the intent of improving its solubility parameter ( e.g. , phosphates , amino acid conjugates , succinates , and sugar conjugates ) . in contrast , the use of ptx prodrugs that are more hydrophobic than ptx itself ( e.g. , cholesteryl carbonate , phospholipid , or fatty acid 
 ester derivatives ) has been explored somewhat . the motivating 
 hypothesis was that these derivatives could be more efficiently loaded 
 into the hydrophobic regions of the various nanocarrier encapsulating 
 vehicles that are water dispersible . notably , a 
 ptx docosahexaenoate ( dha ) ester conjugate has been studied in a phase iii clinical trial . we report here on the chemistry and initial in vitro 
 cytotoxicity 
 properties of a series of taxane silicate derivatives . in particular , 
 the synthesis , hydrolysis rates , and ic50 values of a family 
 of hydrophobic ptx- and dtx - silicate esters [ taxane - si(or)3 ] bearing various r groups differing in their degree of hydrophobicity 
 and steric bulk ( cf . 13 and 4 , respectively ) are described . these constitute a set of 
 promising agents for loading into nanoparticle formulations potentially useful in drug delivery studies . to achieve taxane silicate ester synthesis , 
 we took advantage of 
 the known differences in reactivity of the free hydroxyl groups in 
 ptx or dtx ( scheme 1 ) . for example , the relative 
 rates of derivatization of the three hydroxyl groups in ptx is c2 
 > c7 > c1 , which principally reflects the 
 relative steric hindrance among the three . c was best achieved when triethylamine was used as the base to promote 
 reaction with the appropriate chlorosilane reagent ( 5a  c ) . the preparation of the requisite chlorosilanes 5b,5c,5d , and 6(35 ) is indicated in 
 scheme 1 ( panel c ) ; 5a and 5e are commercially available . use of the hindered tertiary 
 alkylamine rather than pyridine showed greater selectivity for c2-monosilicate 
 ester production with minimal formation of the c2,c7-bis - silicate 
 esters . in the case of the hindered trimenthyloxychlorosilane reagent 
 ( 1d ) , accordingly , 
 we experienced little difficulty in using the less selective catalyst 
 pyridine for the preparation of trimenthyl silicate derivatives . the 
 mixed , tert - butoxy - containing silicates 1f  h were prepared using an excess of the bulky 
 electrophile ( t - buo)2sicl2 ( 6 ) and pyridine as the base . as with the menthyl - containing 
 reagent 1d , we again did not observe competitive reaction 
 at c7 . addition of an excess of ethanol ( for 1f ) or acetic 
 acid ( for 1 g ) to substitute the second chloride ( as well 
 as consume the excess 6 still present ) allowed isolation 
 of the mixed silicates 1f , g , respectively , 
 albeit in overall modest to low yields . on one occasion a small amount 
 of the tri(tert)butyl silicate 1e was 
 isolated from an experiment using an in situ generated ( and less pristine ) 
 lot of the chlorosilane reagent 6 . attempts to prepare 1e using a commercial sample of ( t - buo)3sicl ( 5e ) and pyridine , even at elevated temperatures , 
 gave no evidence of reaction . we presume that 1e was 
 produced by way of the intermediate ptx - si(o - t - bu)2cl followed by subsequent reaction with t - buoh . the ptx c2,c7-bis - silicate esters 2a  c were best prepared using the less hindered 
 pyridine as the 
 base and a larger excess ( 34 equiv ) of the ( ro)3sicl 5a  c . the c7-monosilicate 3a  c derivatives of ptx were accessed 
 by selective hydrolytic cleavage [ trifluoroacetic acid ( tfa ) , h2o , acetone ] of the more labile c2-silicate ester present 
 in the bis - derivatives 2a  c , respectively . similarly , the dtx 2-monosilicate esters 4a  e ( scheme 1 , panel b ) 
 were prepared . in these experiments we chose to use a different tertiary 
 amine , n , n - dimethyl-1-butanamine , 
 and as we conjectured , it showed comparably good c2 vs c7 
 selectivity as triethylamine but a faster reaction rate under otherwise 
 identical conditions . conditions : 
 ( i ) sicl(or)3 ( 5a  d ) , 
 net3 ( for 1a  c ) or py 
 ( for 1d ) , thf ; 
 ( ii ) sicl2(obu)2 ( 6 ) , py , thf ; then etoh ( for 1f or 4e ) or acoh ( for 1 g ) ; ( iii ) sicl(or)3 ( 5a c ) , py , thf ; ( iv ) acetone , 
 water , tfa ( 90/9/1 , v / v / v ) ; ( v ) sicl(or)3 ( 5a  d ) , n - bunme2 ( for 4a  c ) or py ( for 4d ) , thf ; 
 ( vi ) alcohol , rt , pentane ; ( vii ) t - buoh ( 2.1 equiv ) , 
 py , thf . yields of chromatographed taxane silicates : 1a ( 91% ) ; 1b ( 81% ) ; 1c ( 65% ) ; 1d ( 62% ) ; 1e ( 18% ) ; 1f ( 84% ) ; 1 g ( 66% ) ; 2a ( 85% ) ; 2b ( 77% ) ; 2c ( 67% ) ; 3a ( 91% , brsm ) ; 3b ( 66% , brsm ) ; 3c ( 77% , brsm ) ; 4a ( 65% ) ; 4b ( 64% ) ; 4c ( 85% ) ; 4d ( 44% ) ; 4e ( 60% ) . qualitatively , we observed the expected trend that 
 the silicates with greasier alkyl groups traveled faster on silica 
 gel during thin layer and preparative chromatographic experiments . a more quantitative measure of this same trend was observed from measurement 
 of the retention times on a reversed - phase hplc column ( table 1 , column 4 ) . in addition , two empirical indicators 
 of hydrophobicity show similar trends : ( i ) calculated octanol / water 
 partition coefficients ( clogp values , table 1 , column 5 ) and ( ii ) calculated aqueous solubilities ( table 1 , column 6 ) . each retention time was determined 
 by gradient elution from lc / ms on an ( octadecyl)silyl ( ods , c18 ) column 
 [ 5 m , 4.6 ( i.d . )  150 mm ] using a flow rate of 1 ml / min . gradient elution was 56/44% methanol / water to 98/2% methanol / water 
 ( 15 mm nh4oac ) over 15 min followed by an appropriate final 
 hold time . alogp   data shown here ; see supporting 
 information ( table s1 ) for the values from these additional 
 empirical predictors 
 of clogp : ac logp , kowwin , milogp , xlogp3 ; the trends among the values 
 from any of these methods are very similar for all of the predictors . not observed ; elution time of > 60 
 min . we anticipated that 
 these silicates would also differ in their 
 hydrolytic lability given the differences in steric bulk at the silicon 
 atom of the silicate esters across the series . we explored this question 
 by devising a h nmr spectroscopy based method to establish the relative rates of chemical 
 hydrolysis of the derivatives ( table 2 ) . by 
 design , these silicate esters were sufficiently highly hydrophobic 
 to render them only marginally soluble in buffered aqueous solutions . 
 to get meaningful fundamental understanding of the hydrolytic lability 
 under acidic conditions , we deemed it essential to identify a common 
 set of conditions under which each of the silicates would be fully 
 soluble ; that is , homogeneity is paramount . we determined that a 10:1 
 ( v / v ) ratio of acetone / water would solubilize all of these silicates 
 at concentrations suitable for nmr analysis . we then established that 
 use of 1% tfa in this solvent mixture ( measured ph of 1.2 ) at ambient 
 temperature led to rates of silicate ester cleavage that could be 
 conveniently monitored spectroscopically . the change in intensity 
 over time of the chemical shifts of h2 , h3 , h7 and/or 
 the och resonances in the r groups as the silicates 
 were cleaved to release ptx and roh for all silicates 
 not containing a menthyloxy or tert - butoxy moiety 
 ( table 2 , footnote c ) , we saw no evidence for partially hydrolyzed 
 silanol intermediates 
 [ i.e. , ( ro)nsi(oh)4n ] . this suggests that the initial hydrolysis event 
 ( i.e. , cleavage of the first si  or bond ) is the rate - limiting 
 step and that the initially formed monohydroxysilane then degrades , 
 sequentially but faster , to release all of its alcohol moieties , including 
 the free drug . the relative rates of hydrolysis ( krel ) of 14 , normalized 
 to the least 
 reactive silicate , the ptx - menthyloxysilicate 1d , are 
 shown in table 2 . as anticipated , increase 
 in steric bulk of the silicate near the silicon center slows its hydrolysis 
 rate . the krel values differ by > 2000 
 between the extremes of the triethyl ptx - silicate 1a vs 
 the hindered trimenthyl silicate ester 1d . the hydrolysis 
 rates for the triethyl vs trioctyl silicates 1a vs 1b ( for ptx ) or 4a vs 4b were similar 
 ( difference in krel of 3 ) , which 
 shows that the hydrophobicity of the silicate can be significantly 
 altered with only a small accompanying change in the relative hydrolysis 
 rate . ptx - silicates at the more hindered c7-position hydrolyzed approximately 
 715 times more slowly than those at c2. moreover , 
 ( i ) the rate difference for cleavage of silicates at these two sites 
 increased slightly as the bulk of the alkyl groups increased in the 
 series of ethyl to n - octyl to isopropyl and ( ii ) 
 the trends were the same whether comparing the differences at c7 vs 
 c2 for both the monosilicates ( 1a vs 3a , 1b vs 3b , and 1c vs 3c ) and those same sites within each of the bis - silicates 2a  c . each silicate in 
 a solution of acetone - d6/d2o / cf3co2h ( volume ratio of 90:9:1 ) at a concentration 
 of 0.01 m was 
 kept at 22 c and the reaction progress monitored periodically 
 and continuously by h nmr spectroscopy . the krel values are benchmarked relative to that of the ptx - trimenthyloxy 
 derivative 1d , the ptx - silicate having the slowest observed 
 rate of hydrolysis . nmr 
 analysis suggested the presence 
 of steady - state levels ( typically 10% ) of intermediate , partially 
 cleaved silicates [ i.e. , ( ro)4nsi(oh)n , where n = 13 ] , 
 which underwent further clean conversion of the fully hydrolyzed alcohols , 
 including the taxane . acetyl 
 ( ch3co ) , which 
 is part of an acetoxy substituent on the silicate oxygen atom . cytotoxicity of the ptx - silicates 13 and dtx - silicates 4 was 
 examined against mda - mb-231 
 cells ( table 3 ) . we used this as a model cell 
 line representing triple negative breast cancer , a malignancy for 
 which taxanes are used as front - line agents . silicates having faster 
 rates of hydrolysis ( table 2 ) tend to show 
 cytotoxicities similar to those of the parent taxane . this suggests 
 that the silicate esters are hydrolyzed back to ptx or dtx either 
 in the culture medium or inside the cell during the course of the 
 assay . cell viability was measured after 
 72 h. the reported data 
 are the median 
 values for the distribution of ic50 values falling within 
 the 95% confidence interval . the strategy provides the ability to control both the hydrophobicity 
 and the hydrolysis rate of these drug derivatives . each of these features 
 provides a mechanism through which drug encapsulation and release 
 properties into and from nanoparticles can likely be tuned . we have 
 determined relative rates of hydrolysis of these silicates via h nmr spectroscopic analysis . silicates 1a  c , 2a , 3a , and 4a  c all showed ic50 values similar to that of their 
 parent taxane , suggesting hydrolysis in the culture medium and/or 
 inside the cell . the ic50 values spanned a range of 10 for each of the ptx and dtx family of taxanes . certain of 
 these silicates are being further evaluated here for their ability 
 to form small , stable , block - copolymer - based nanoparticles as potential 
 drug - delivery constructs . the known tri - n - octyloxychlorosilane , triisopropoxychlorosilane , trimenthyloxychlorosilane , and di - tert - butoxydichlorosilane were synthesized from silicon tetrachloride and n - octanol , isopropanol , ( )-menthol , and tert - butanol ( the liquids , each dried over activated 3  
 molecular sieves overnight ) , respectively . ethanol ( anhydrous ) 
 was further dried by storing overnight over activated 3  molecular 
 sieves . ethyl acetate ( etoac , acs grade ) and hexanes ( acs grade ) were 
 used as received . the acetone - d6 and chloroform - d were dried over activated 3  molecular sieves overnight . all thin layer chromatography 
 ( tlc ) data were collected on glass- or plastic - backed plates coated 
 with f-254 indicator . visualization was done by uv light and/or staining 
 with phosphomolybdic acid ( pma ) . medium pressure liquid chromatography 
 ( mplc ) purifications were performed using columns dry - packed with 
 approximately 2535 m silica gel . compound detection was 
 performed by using a uv absorbance detector at 254 nm and a differential 
 refractometer in series . each silicate ester was purified by mplc , 
 under conditions that achieved effective separation of starting taxane , 
 monosilicate , and bis - silicate esters , shortly before being used in 
 the cytotoxicity study . each compound whose cytotoxicity is reported 
 in table 3 was purified in this fashion , at 
 which point it was shown to be of > 95% purity by hplc analysis 
 in 
 a c18- or c8-reversed phase column . all h characterization spectra were taken 
 in cdcl3 , and chemical shifts (  ) are referenced 
 to tetramethylsilane at  = 0.00 . all c nmr characterization 
 spectra were taken in cdcl3 on either a 125 mhz ( c ) or a 75 mhz ( c ) instrument and referenced to chcl3 at  = 77.23 . the following abbreviations are used 
 to describe the nmr signals : s ( singlet ) , d ( doublet ) , t ( triplet ) , 
 q ( quartet ) , sept ( septet ) , m ( multiplet ) , br ( broad ) , and app ( apparent ) . high resolution 
 mass spectra were collected on an esi - tof instrument using poly(ethylene 
 glycol ) ( peg ) or poly(propylene glycol ) ( ppg ) as an internal standard . all samples 
 were collected in attenuated total reflectance ( atr ) mode as thin 
 films on a germanium window . paclitaxel 
 ( 55.3 mg , 0.0648 mmol , 1.0 equiv ) 
 was dissolved in dry thf ( 1.0 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . triethylamine ( 20 l , 
 0.130 mmol , 2.0 equiv ) was added by wiretrol . triethoxychlorosilane 
 ( 5a ) ( 25 l , 0.0127 mmol , 2.0 equiv ) was then added , 
 and a white precipitate was immediately observed . the culture tube 
 was sealed , and the suspension was allowed to stir for 1 h at room 
 temperature . the reaction slurry was diluted with a mixture of hexanes / etoac 
 ( 1:1 ) and filtered through a short plug of celite to remove the triethylammonium 
 salt . the filtrate was concentrated under reduced pressure , and the 
 residue was redissolved in a mixture of hexanes / etoac ( 1:1 ) . chromatography 
 ( sio2 , 1:1 hexanes / etoac ) via mplc yielded the title compound 
 as a white , crystalline solid ( 59.6 mg , 0.0587 mmol , 90.6% ) . h nmr ( 500 mhz , cdcl3 ) :  8.12 ( dd , j = 8.5 , 1.4 hz , 2h , c2o2c - o - ph ) , 7.78 ( dd , j = 8.5 , 1.3 hz , 2h , c3nhco - o - ph ) , 7.62 ( tt , j = 7.5 , 1.2 hz , 1h , c2o2c - p - ph ) , 7.567.46 ( m , 3h , c2o2c - m - ph and c3nhco - p - ph ) , 7.437.36 ( m , 6h , c3-o - ph , 
 c3-m - ph , and c3nhco - m - ph ) , 7.29 ( tt , j = 6.5 , 2.2 hz , 1h , c3-p - ph ) , 7.19 ( d , j = 8.6 hz , 1h , c3nh ) , 
 6.28 ( s , 1h , h10 ) , 6.24 ( br dd , j = 9 , 9 hz , 1h , 
 h13 ) , 5.72 ( dd , j = 8.5 , 3.2 hz , 1h , h3 ) , 
 5.68 ( d , j = 7.1 hz , 1h , h2 ) , 4.97 ( dd , j 
 = 9.4 , 2.0 hz , 1h , h5 ) , 4.96 ( d , j = 3.3 
 hz , 1h , h2 ) , 4.43 ( ddd , j = 10.9 , 6.4 , 4.5 
 hz , 1h , h7 ) , 4.32 ( d , j = 8.5 hz , 1h , h20 ) , 
 4.20 ( d , j = 8.5 hz , 1h , h20 ) , 3.80 ( d , j = 7.2 hz , 1h , h3 ) , 3.71 [ q , j = 7.0 hz , 
 6h , c2osi(och2ch3)3 ] , 2.56 ( ddd , j = 14.7 , 
 9.6 , 6.5 hz , 1h , h6 ) , 2.45 ( s , 3h , c4oac ) , 2.44 ( br s , 1h , 
 c7oh ) , 2.32 ( dd , j = 15.4 , 9.4 , hz , 1h , h14 ) , 
 2.24 ( s , 3h , c10oac ) , 2.08 ( dd , j = 15.2 , 8.8 hz , 
 1h , h14 ) , 1.90 ( d , j = 1.2 hz , 3h , c18h3 ) , 1.89 ( ddd , j = 14.5 , 11.0 , 2.4 hz , 1h , 
 h6 ) , 1.68 ( s , 3h , c19h3 ) , 1.64 ( br s , 1h , c1oh ) , 
 1.24 ( s , 3h , c17h3 ) , 1.15 [ t , j = 7.0 
 hz , 9h , c2osi(och2ch3)3 ] , and 1.13 ( s , 3h , c16h3 ) . c nmr ( 75 mhz , cdcl3 ) :  204.0 , 
 171.6 , 171.0 , 170.1 , 167.3 , 167.2 , 143.0 , 138.2 , 134.2 , 133.9 , 132.9 , 
 132.0 , 130.4 , 129.3 , 128.9 ( 2 ) , 128.8 , 128.2 , 127.3 , 126.8 , 
 84.6 , 81.2 , 79.3 , 76.7 , 75.8 , 75.3 , 75.1 , 72.3 , 71.5 , 59.7 , 58.7 , 
 55.6 , 45.7 , 43.4 , 35.7 , 35.6 , 27.0 , 23.0 , 22.4 , 21.1 , 18.2 , 14.9 , 
 and 9.8 . hrms ( esi ) calcd for c53h65nnao17si [ m + na ] 1038.3914 , found 1038.3942 . ir ( thin 
 film ) 3500 ( br ) , 2977 , 2898 , 1744 , 1730 , 1636 , 1580 , 1540 , 1487 , 1452 , 
 1371 , 1314 , 1268 , 1240 , 1170 , 1145 , 1078 , 1025 , 978 , 908 , 854 , 797 , 
 and 710 cm . paclitaxel ( 76.0 mg , 0.0890 mmol , 1.0 equiv ) 
 was dissolved in dry thf ( 1.5 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . triethylamine ( 60 l , 
 0.430 mmol , 4.8 equiv ) was added by wiretrol . a 1.67:1 mixture of 
 tri - n - octyloxychlorosilane ( 5b)/tetra - n - octyloxysilane ( 0.200 
 mg , 0.257 mmol , 2.9 equiv of tri - n - octyloxychlorosilane ) 
 was added , and a white precipitate was immediately observed . the culture 
 tube was capped , and the suspension was allowed to stir for 22 h at 
 room temperature . the reaction slurry was diluted with a mixture of 
 hexanes / etoac ( 1:1 ) , the slurry filtered through a short plug of celite 
 to remove the triethylammonium salt , the filtrate concentrated under 
 reduced pressure , and the residue redissolved in a mixture of hexanes / etoac 
 ( 2:1 ) . chromatography ( sio2 , 2:1 hexanes / etoac ) via mplc 
 yielded the title compound as a white , crystalline solid ( 91.5 mg , 
 0.0721 mmol , 81.0% ) . h nmr ( 500 mhz , cdcl3 ) : 
  8.13 ( dd , j = 8.5 , 1.5 hz , 2h , c2o2c - o - ph ) , 7.77 ( dd , j = 8.5 , 1.4 
 hz , 2h , c3nhco - o - ph ) , 7.62 ( tt , j 
 = 7.4 , 1.3 hz , 1h , c2o2c - p - ph ) , 
 7.557.46 ( m , 3h , c2o2c - m - ph and 
 c3nhco - p - ph ) , 7.437.35 ( m , 6h , c3-o - ph , c3-m - ph , and c3nhco - m - ph ) , 7.28 ( tt , j = 6.9 , 1.7 hz , 1h , c3-p - ph ) , 7.19 ( d , j = 8.6 hz , 1h , c3nh ) , 
 6.28 ( s , 1h , h10 ) , 6.25 ( br dd , j = 9 , 9 hz , 1h , 
 h13 ) , 5.72 ( dd , j = 8.6 , 3.2 hz , 1h , h3 ) , 
 5.68 ( d , j = 7.1 hz , 1h , h2 ) , 4.97 ( dd , j 
 = 9.8 , 2.1 hz , 1h , h5 ) , 4.96 ( d , j = 3.2 
 hz , 1h , h2 ) , 4.44 ( ddd , j = 10.9 , 6.7 , 4.2 
 hz , 1h , h7 ) , 4.31 ( d , j = 8.4 hz , 1h , h20 ) , 
 4.20 ( d , j = 8.3 hz , 1h , h20 ) , 3.80 ( d , j = 7.1 hz , 1h , h3 ) , 3.61 { t , j = 6.8 hz , 
 6h , c2osi[och2(ch2)6ch3]3 } , 2.56 ( ddd , j = 14.8 , 9.6 , 6.6 hz , 1h , h6 ) , 2.47 ( d , j = 4.1 hz , 1h , c7oh ) , 2.44 ( s , 3h , c4oac ) , 2.32 ( dd , j = 15.4 , 9.4 hz , 1h , h14 ) , 2.24 ( s , 3h , c10oac ) , 
 2.07 ( dd , j = 15.4 , 8.8 hz , 1h , h14 ) , 1.89 
 ( d , j = 1.4 hz , 3h , c18h3 ) , 1.89 ( m , 1h , 
 h6 ) , 1.68 ( s , 3h , c19h3 ) , 1.65 ( br s , 1h , c1oh ) , 
 1.48 [ tt , j = 6.9 , 6.9 hz , 6h , c2osi(och2ch2(ch2)5ch3)3 ] , 1.321.22 { m , 33h , 
 c2osi[och2ch2(ch2)5ch3]3 and 
 c17h3 } , 1.13 ( s , 3h , c16h3 ) , and 0.88 { t , j = 6.9 hz , 9h , c2osi[och2ch2(ch2)5ch3]3}. c nmr ( 75 mhz , cdcl3 ) :  204.0 , 171.5 , 170.9 , 170.1 , 167.2 , 167.2 , 143.0 , 138.3 , 
 134.3 , 133.9 , 132.9 , 132.0 , 130.4 , 129.3 , 128.9 ( x2 ) , 128.8 , 128.1 , 
 127.3 , 126.8 , 84.7 , 81.2 , 79.3 , 76.6 , 75.8 , 75.3 , 74.9 , 72.4 , 71.4 , 
 64.1 , 58.7 , 55.5 , 45.7 , 43.4 , 35.8 , 35.7 , 32.4 , 32.0 , 29.54 , 29.52 , 
 27.0 , 25.8 , 23.0 , 22.9 , 22.4 , 21.1 , 14.9 , 14.3 , and 9.8 . hrms ( esi ) 
 calcd for c71h101nnao17si [ m + na ] 1290.6731 ; found 1290.6749 . ir ( thin film ) 2926 , 2855 , 1730 , 
 1665 , 1643 , 1602 , 1581 , 1518 , 1484 , 1453 , 1371 , 1312 , 1271 , 1240 , 
 1174 , 1094 , 1025 , 985 , 926 , 907 , 851 , 801 , 777 , and 711 cm . paclitaxel ( 38.8 mg , 0.0454 mmol , 1.0 equiv ) 
 was dissolved in dry thf ( 1.0 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . triethylamine ( 25 l , 
 0.179 mmol , 3.9 equiv ) was added by wiretrol . a 2.9:1 mixture of triisopropoxychlorosilane 
 ( 5c)/tetraisopropoxysilane 
 ( 0.155 mg , 0.132 mmol , 2.9 equiv of triisopropoxychlorosilane ) 
 was added . the culture tube was capped , and a white precipitate was 
 observed within minutes . the suspension was stirred at room temperature 
 for 48 h , and the cloudy , heterogeneous reaction mixture was noted 
 to be slightly yellowed . the suspension was diluted with a mixture 
 of hexanes / etoac ( 1:1 ) , the slurry filtered through a short plug of 
 celite to remove the triethylammonium salt , the filtrate concentrated 
 under reduced pressure , and the residue redissolved in a mixture of 
 hexanes / etoac ( 1:1 ) . chromatography ( sio2 , 1:1 hexanes / ethyl 
 acetate ) via mplc yielded the title compound as a white , crystalline 
 solid ( 31.1 mg , 0.0294 mmol , 64.7% ) . h nmr ( 500 mhz , cdcl3 ) :  8.11 ( dd , j = 8.5 , 1.4 hz , 2h , 
 c2o2c - o - ph ) , 7.79 ( dd , j = 8.4 , 1.3 hz , 2h , c3nhco - o - ph ) , 7.62 ( tt , j = 7.6 , 1.3 hz , 1h , c2o2c - p - ph , 1h ) , 7.557.47 ( m , 3h , c2o2c - m - ph and c3nhco - p - ph ) , 7.447.35 ( m , 
 6h , c3-o - ph , c3-m - ph , and c3nhco - m - ph ) , 7.27 ( tt , j = 7.0 , 1.7 hz , 1h , c3-p - ph ) , 
 7.17 ( d , j = 8.5 hz , 1h , c3nh ) , 6.28 ( s , 
 1h , h10 ) , 6.19 ( br dd , j = 9 , 9 hz , 1h , h13 ) , 5.69 
 ( dd , j = 8.5 , 3.6 hz , 1h , h3 ) , 5.68 ( d , j = 6.7 hz , 1h , h2 ) , 4.98 ( d , j = 3.6 hz , 
 1h , h2 ) , 4.96 ( dd , j = 9.7 , 2.4 hz , 1h , h5 ) , 
 4.44 ( ddd , j = 10.9 , 6.6 , 4.1 hz , 1h , h7 ) , 4.31 ( d , j = 8.4 hz , 1h , h20 ) , 4.20 ( d , j = 8.4 hz , 1h , h20 ) , 4.13 { sept , j = 6.1 hz , 
 3h , c2osi[och(ch3)2]3 } , 3.80 ( d , j = 7.1 hz , 1h , h3 ) , 2.56 
 ( ddd , j = 14.8 , 9.8 , 6.6 hz , 1h , h6 ) , 2.47 
 ( d , j = 4.1 hz , 1h , c7oh ) , 2.42 ( s , 3h , c4oac ) , 2.29 
 ( dd , j = 15.4 , 9.4 hz , 1h , h14 ) , 2.24 ( s , 
 3h , c10oac ) , 2.06 ( dd , j = 15.4 , 8.9 hz , 1h , h14 ) , 
 1.91 ( d , j = 1.4 hz , 3h , c18h3 ) , 1.88 
 ( ddd , j = 14.3 , 11.0 , 2.4 hz , 1h , h6 ) , 1.76 
 ( br s , 1h , c1oh ) , 1.68 ( s , 3h , c19h3 ) , 1.23 ( s , 3h , c17h3 ) , 1.15 { d , j = 6.1 hz , 9h , c2osi[och(ch3)a(ch3)b]3 } , 1.12 { d , j = 6.1 hz , 9h , c2osi[och(ch3)a(ch3)b]3 } , and 1.12 ( s , 3h , c16h3 ) . c nmr ( 125 mhz , cdcl3 ) :  204.1 , 171.5 , 
 171.1 , 170.1 , 167.3 , 167.2 , 143.1 , 138.3 , 134.4 , 133.9 , 132.9 , 131.9 , 
 130.4 , 129.4 , 128.9 ( x2 ) , 128.8 , 128.1 , 127.3 , 127.0 , 84.7 , 81.2 , 
 79.3 , 76.7 , 75.9 , 75.3 , 74.9 , 72.3 , 71.5 , 66.7 , 58.7 , 55.8 , 45.7 , 
 43.4 , 35.8 , 35.7 , 27.0 , 25.44 , 25.42 , 23.0 , 22.4 , 21.1 , 15.2 , and 
 9.8 . hrms ( esi ) calcd for c56h71nnao17si [ m + na ] 1080.4383 ; found 1080.4380 . ir ( thin film ) 
 3500 ( br ) , 2974 , 2934 , 1729 , 1666 , 1603 , 1583 , 1515 , 1485 , 1452 , 1371 , 
 1313 , 1269 , 1241 , 1174 , 1114 , 1052 , 985 , 897 , 850 , 800 , 773 , and 712 
 cm . paclitaxel ( 95.0 mg , 0.111 mmol , 1.0 equiv ) 
 was dissolved in dry 
 thf ( 8.0 ml ) in an oven - dried culture tube fitted with a teflon - lined 
 cap and magnetic stir bar . pyridine ( 100 l , 1.24 mmol , 11.2 
 equiv ) was added by wiretrol . trimenthyloxychlorosilane ( 5d ) , judged to contain 90% of the chlorosilane 
 ( 579.1 mg , 0.986 mmol , 8.9 equiv ) by h nmr analysis , was 
 added by wiretrol . the culture tube was capped , and the suspension 
 was allowed to stir for 12 h at 45 c . the solid residue was triturated 
 with a mixture of hexanes / etoac ( 3:1 ) , and the resulting slurry was 
 filtered through a short plug of celite to remove the pyridinium salt . the filtrate was concentrated under reduced pressure , and the residue 
 was purified by mplc ( sio2 , 3:1 hexanes / etoac ) to yield 
 the title compound as a white , crystalline solid ( 94.2 mg , 0.069 mmol , 
 62% ) . h nmr ( 500 mhz , cdcl3 ) :  8.11 
 ( dd , j = 8.3 , 1.3 hz 2h , o2c - o - ph , 7.77 ( dd , j = 8.1 , 1.0 hz , 2h , c3nhco - o - ph ) , 7.60 ( tt , j = 7.4 , 1.3 hz , 1h , c2o2c - p - ph ) , 7.537.47 ( m , 3h , c2o2c - m - ph and c3nhco - p - ph ) , 7.437.36 ( m , 6h , c3-o - ph , 
 c3-m - ph , and c3nhco - m - ph ) , 7.30 ( tt , j = 7.0 , 1.6 hz , 1h , c3-p - ph ) , 7.11 ( d , j = 8.5 hz , 1h , c3nh ) , 
 6.28 ( s , 1h , h10 ) , 6.22 ( ddq , j = 10.3 , 9.3 , 1.4 
 hz , 1h , h13 ) , 5.72 ( dd , j = 8.5 , 3.5 hz , 1h , h3 ) , 
 5.68 ( d , j = 7.1 hz , 1h , h2 ) , 5.10 ( d , j 
 = 3.5 hz , 1h , h2 ) , 4.97 ( dd , j = 9.6 , 2.3 hz , 1h , h5 ) , 4.45 ( ddd , j = 10.8 , 6.7 , 
 4.1 hz , 1h , h7 ) , 4.30 ( dd , j = 8.6 , 0.9 hz , 1h , h20 ) , 
 4.20 ( d , j = 8.5 , 1.1 hz , 1h , h20 ) , 3.80 ( d , j = 7.1 hz , 1h , h3 ) , 3.64 ( ddd , j = 10.6 , 
 10.6 , 4.3 hz , 3h , h1menth ) , 2.57 ( ddd , j = 14.8 , 9.8 , 6.6 hz , 1h , h6 ) , 2.48 ( d , j = 4.1 hz , 1h , c7oh ) , 2.39 ( s , 3h , c4oac ) , 2.30 ( dd , j = 15.3 , 9.5 hz , 1h , h14 ) , 2.25 ( s , 3h , c10oac ) , 2.20 ( dsep , j = 2.6 , 7.0 hz , 3h , h7menth ) , 2.12 ( dd , j = 15.9 , 9.0 hz , 1h , h14 ) , 1.921.86 ( m , 
 4h , h6eqmenth and h6 ) , 1.88 ( d , j = 1.3 hz , 3h , h18 = cch3 ) , 1.80 ( s , 1h , c1oh ) , 
 1.68 ( s , 3h , h19 o = ccch3 ) , 1.61 ( m , 3h , h4eqmenth ) , 1.58 ( dddd , j = 13.0 , 3.0 , 3.0 , 3.0 
 hz , h3eqmenth ) , 1.281.24 ( m , 6h , h5menth ) , 1.25 ( s , 3h , c(me)c16h3 ) , 1.161.10 ( dddd , 3h , j = 11.2 , 11.2 , 2.8 , 2.8 hz h2menth ) , 1.14 [ s , 
 3h , c(me)c17h3 ] , 0.92 ( ddd , j = 12 , 12 , 
 12 hz , 3h , h6axmenth ) , 0.910.85 ( m , 3h , h3axmenth ) , 0.87 ( d , 9h , j = 7.1 hz , h8menth ) , 0.83 ( d , j = 6.6 hz , 9h , h10menth ) , 
 0.830.77 ( dddd , j = 12.3 , 12.3 , 12.3 , 3.0 
 hz , 3h , h4axmenth ) , and 0.74 ( d , j = 6.9 
 hz , 9h , h9menth ) . c nmr ( 125 mhz , cdcl3 ) :  204.1 , 171.6 , 170.7 , 170.0 , 167.2 , 167.1 , 143.2 , 
 138.1 , 134.2 , 133.8 , 132.6 , 132.0 , 130.4 , 129.3 , 129.0 , 128.9 , 128.8 , 
 128.1 , 127.3 , 126.9 , 84.7 , 81.1 , 79.3 , 76.7 , 75.8 , 75.3 , 74.5 , 74.2 , 
 71.4 ( c1menth ) , 71.36 , 58.7 , 55.5 , 49.7 ( c2menth ) , 45.6 , 45.0 ( c7menth ) , 43.4 , 35.9 , 35.7 , 34.5 ( c5menth ) , 31.7 ( c6menth ) , 27.0 , 25.4 ( c3menth ) , 22.9 ( c4menth ) , 22.7 , 22.5 ( c8menth ) , 22.4 , 
 21.4 ( c9menth ) , 21.1 , 15.8 ( c10menth ) , 15.1 , 
 and 9.8 . hrms ( esi ) calcd for c67h103nnao17si [ m + na ] 1368.7206 ; found 1368.7275 . ir ( thin 
 film ) 3443 , 2953 , 2925 , 2870 , 1762 , 1718 , 1496 , 1452 , 1368 , 1316 , 
 1274 , 1245 , 1162 , 1108 , 1083 , 1070 , 1052 , 1026 , 987 , 890 , 765 , and 
 751 cm . tlc rf ( 9:1 hexanes / etoac ) = 0.20 . paclitaxel ( ptx , 49.8 mg , 0.0583 mmol , 
 1.0 equiv ) was dissolved in dry thf ( 1.0 ml ) in an oven - dried culture 
 tube with a teflon - lined cap and magnetic stir bar . in a separate 
 oven - dried culture tube fitted with a teflon - lined cap , sicl4 ( 0.40 ml , 2.6 mmol ) , pyridine ( 0.84 ml , 10.4 mmol ) , tert - butanol ( 0.73 ml , 7.6 mmol ) , and thf ( 10 ml ) were combined , 
 and the mixture was stirred for 24 h. a 1 ml aliquot of this silylating 
 reagent mixture was added to the tube containing ptx . the culture 
 tube was capped , and the solution was allowed to stir at room temperature 
 overnight . to the resulting suspension , additional pyridine ( 50 l , 
 0.62 mmol , 13 equiv ) and glacial acetic acid ( 50 l , 0.87 mmol , 
 24 equiv ) were added . the mixture was allowed to stir for an additional 
 48 h at room temperature . the slurry was filtered through a short plug of celite to remove 
 the pyridinium salt . the filtrate was concentrated under reduced pressure , 
 and the residue was redissolved in a mixture of hexanes / etoac ( 2:1 ) . chromatography ( sio2 , 2:1 hexanes / etoac ) via mplc yielded 1e ( 11.2 mg , 0.0107 mmol , 18.4% ) . material collected from 
 two later eluting fractions gave mass spectral evidence for the chloride 
 ptx - si(o - t - bu)2cl ( 23.0 mg , 0.0212 mmol , 
 36.3% ) and the silanol ptx - si(o - t - bu)2oh ( 8.6 mg , 0.0078 mmol , 13.4% ) . h nmr ( 500 mhz , cdcl3 ) :  8.11 ( dd , j = 8.8 , 1.7 hz , 2h , 
 c2o2c - o - ph ) , 7.78 ( dd , j = 8.8 , 1.8 hz , 2h , c3nhco - o - ph ) , 7.61 ( tt , j = 7.3 , 1.2 hz , 1h , c2o2c - p - ph , 1h ) , 7.567.34 ( m , 9h , c2o2c - m - ph , c3nhco - p - ph , c3-o - ph , c3-m - ph , and c3nhco - m - ph ) , 7.307.24 ( m , 1h , c3-p - ph ) , 7.05 ( d , j = 8.5 hz , 1h , c3nh ) , 6.29 
 ( s , 1h , h10 ) , 6.17 ( br dd , j = 9 , 9 hz , 1h , h13 ) , 
 5.745.66 ( m , 2h , h2 and h3 ) , 5.16 ( d , j = 2.9 hz , 1h , h2 ) , 4.97 ( dd , j = 9.2 , 2.3 
 hz , 1h , h5 ) , 4.45 ( app br dd , j = 11 , 6 hz , 1h , h7 ) , 
 4.31 ( d , j = 8.4 hz , 1h , h20 ) , 4.20 ( d , j = 8.6 hz , 1h , h20 ) , 3.80 ( d , j = 7.0 hz , 1h , h3 ) , 2.57 ( ddd , j = 15.2 , 9.9 , 6.7 
 hz , 1h , h6 ) , 2.47 ( br d , j = 4 hz , 1h , c7oh ) , 
 2.42 ( s , 3h , c4oac ) , 2.32 ( dd , j = 15.9 , 9.6 , hz , 
 1h , h14 ) , 2.25 ( s , 3h , c10oac ) , 2.17 ( br dd , j = 14 , 5 hz , 1h , h14 ) , 1.93 ( br d , j = 1 hz , 
 3h , c18h3 ) , 1.89 ( br m , 1h , h6 ) , 1.78 ( br s , 1h , 
 c1oh ) , 1.68 ( s , 3h , c19h3 ) , 1.24 { overlapping s , 27h , c2osi[oc(ch3)3]3 and s , 3h , c17h3 } , and 1.13 ( s , 3h , c16h3 ) . c nmr ( 125 mhz , cdcl3 ) :  204.1 , 171.6 , 
 171.1 , 170.1 , 167.4 , 167.2 , 143.2 , 138.3 , 134.5 , 133.9 , 132.8 , 131.9 , 
 130.4 , 129.4 , 128.97 , 128.95 , 128.8 , 128.0 , 127.3 , 126.9 , 84.7 , 81.2 , 
 79.3 , 76.7 , 75.9 , 75.3 , 74.2 , 73.9 , 72.4 , 71.4 , 58.7 , 55.5 , 45.7 , 
 43.4 , 36.0 , 35.7 , 31.4 , 27.0 , 23.0 , 22.4 , 21.1 , 15.3 , and 9.8 . ir 
 ( thin film ) 3500 ( br ) , 2973 , 2929 , 1729 , 1670 , 1511 , 1483 , 1452 , 1389 , 
 1367 , 1268 , 1242 , 1183 , 1124 , 1069 , 1025 , 985 , 835 , 800 , 758 , and 
 711 cm . hrms ( esi ) calcd for c59h77nnao17si [ m + na ] 1122.4853 ; found 
 1122.4901 . paclitaxel ( 49.3 mg , 0.0577 mmol , 1.0 equiv ) 
 was dissolved in dry thf ( 1.0 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . pyridine ( 0.12 ml , 
 1.48 mmol , 26 equiv ) was added by syringe . a distilled sample of di - tert - butoxydichlorosilane ( 6 ) ( 0.349 mg , 1.42 mmol , 25 equiv ) was added by wiretrol . 
 the culture tube was sealed , and the solution was allowed to stir 
 at room temperature . a small amount of a white precipitate was observed 
 after 30 min , and the reaction mixture was noted to be cloudy 
 and heterogeneous after stirring for 6 h. to this suspension , additional 
 pyridine ( 0.47 ml , 5.81 mmol , 100 equiv ) and anhydrous ethanol ( dried 
 overnight over 3  molecular sieves , 0.68 ml , 11.7 mmol , 200 
 equiv ) were added . the mixture was allowed to stir for an additional 
 1 h at room temperature . the suspension was diluted with a mixture 
 of hexanes / etoac ( 1:1 ) . the slurry was filtered through a short plug 
 of celite to remove the pyridinium salt . the filtrate was concentrated 
 under reduced pressure , and the residue was redissolved in a mixture 
 of hexanes / etoac ( 2:1 ) . chromatography ( sio2 , 2:1 hexanes / etoac ) 
 via mplc yielded the title compound as a white , crystalline solid 
 ( 52.0 mg , 0.0485 mmol , 84.1% ) . h nmr ( 500 mhz , cdcl3 ) :  8.11 ( dd , j = 8.5 , 1.4 hz , 2h , 
 c2o2c - o - ph ) , 7.79 ( dd , j = 8.4 , 1.4 hz , 2h , c3nhco - o - ph ) , 7.62 ( tt , j = 7.4 , 1.3 hz , 1h , c2o2c - p - ph , 1h ) , 7.567.46 ( m , 3h , c2o2c - m - ph and c3nhco - p - ph ) , 7.457.33 ( m , 
 6h , c3-o - ph , c3-m - ph , and c3nhco - m - ph ) , 7.307.22 
 ( m , 1h , c3-p - ph ) , 7.15 ( d , j = 8.4 hz , 1h , c3nh ) , 6.28 ( s , 1h , h10 ) , 6.18 ( br dd , j = 9 , 9 hz , 1h , h13 ) , 5.68 ( d , j = 7.2 
 hz , 1h , h2 ) , 5.66 ( dd , j = 8.3 , 3.6 hz , 1h , h3 ) , 
 5.01 ( d , j = 3.6 hz , 1h , h2 ) , 4.97 ( dd , j = 9.7 , 2.3 hz , 1h , h5 ) , 4.44 ( ddd , j = 10.8 , 6.6 , 4.1 hz , 1h , h7 ) , 4.31 ( d , j = 8.4 hz , 
 1h , h20 ) , 4.19 ( d , j = 8.4 hz , 1h , h20 ) , 
 3.79 ( d , j = 7.0 hz , 1h , h3 ) , 3.64 ( q , j 
 = 7.0 hz , 2h , c2osioch2ch3 ) , 2.56 ( ddd , j = 14.8 , 
 9.7 , 6.6 hz , 1h , h6 ) , 2.45 ( d , j = 4.1 hz , 
 1h , c7oh ) , 2.41 ( s , 3h , c4oac ) , 2.28 ( dd , j = 15.4 , 
 9.4 , hz , 1h , h14 ) , 2.24 ( s , 3h , c10oac ) , 2.05 ( dd , j = 15.3 , 9.0 hz , 1h , h14 ) , 1.90 ( d , j = 1.4 hz , 3h , c18h3 ) , 1.88 ( ddd , j = 14.4 , 
 11.1 , 2.5 hz , 1h , h6 ) , 1.68 ( s , 4h , c1oh and c19h3 ) , 1.26 ( s , 9h , c2osioc(ch3)2 ] , 1.25 ( s , 9h , c2osioc(ch3)2 ] , 1.23 ( s , 3h , c17h3 ) , and 1.13 ( overlapping t , j = 7.0 hz , 3h , 
 c2osich2ch3 and s , 3h , c16h3 ) . c nmr ( 125 mhz , 
 cdcl3 ) :  204.1 , 171.5 , 171.0 , 170.0 , 167.3 , 167.2 , 
 143.1 , 138.4 , 134.4 , 133.9 , 132.8 , 131.9 , 130.4 , 129.4 , 128.90 , 128.89 , 
 128.8 , 128.1 , 127.3 , 127.0 , 84.7 , 81.2 , 79.3 , 76.6 , 75.9 , 75.3 , 74.9 , 
 73.99 , 73.98 , 72.3 , 71.4 , 59.3 , 58.7 , 55.8 , 45.7 , 43.4 , 35.8 , 35.7 , 
 31.41 , 31.38 , 27.0 , 22.9 , 22.3 , 21.1 , 18.2 , 15.1 , and 9.8 . ir ( thin 
 film ) 3500 ( br ) , 2976 , 2936 , 1726 , 1665 , 1603 , 1582 , 1514 , 1485 , 1452 , 
 1389 , 1368 , 1312 , 1270 , 1242 , 1179 , 1128 , 1069 , 1025 , 981 , 909 , 853 , 
 821 , 800 , 775 , 733 , and 711 cm . hrms ( esi ) calcd 
 for c57h73nnao17si [ m + na ] 1094.4540 ; found 1094.4579 . tlc rf ( 2:1 hexanes / etoac ) = 0.2 . paclitaxel ( 33.5 mg , 0.0392 mmol , 1.0 equiv ) 
 was dissolved in thf ( 1.0 ml , dried by distillation from sodium / benzophenone ) 
 in an oven - dried culture tube with a teflon - lined cap and magnetic 
 stir bar . pyridine ( 50 l , 0.618 mmol , 16 equiv ) was added by 
 wiretrol . a distilled sample of di - tert - butoxydichlorosilane 
 ( 6 ) ( 0.0524 mg , 0.214 mmol , 
 5.5 equiv ) was added by wiretrol . the culture tube was sealed , and 
 the solution was allowed to stir at room temperature for 24 h. the 
 reaction mixture was noted to be cloudy and heterogeneous after stirring 
 overnight . to the suspension , pyridine was again added ( 50 l , 
 0.618 mmol , 16 equiv ) . immediately afterward , glacial acetic acid 
 ( 50 l , 0.873 mmol , 22 equiv ) was added . the mixture was allowed 
 to stir for an additional 24 h at room temperature . the reaction suspension 
 was diluted with etoac , the slurry filtered through a short plug of 
 celite to remove the pyridinium salt , the filtrate concentrated under 
 reduced pressure , and the residue redissolved in a mixture of hexanes / etoac 
 ( 2:1 ) . purification ( sio2 , 2:1 hexanes / etoac ) using mplc 
 yielded the title compound ( 28.0 mg , 0.0258 mmol , 65.8% ) . h nmr ( 500 mhz , cdcl3 ) :  8.13 ( dd , j = 8.5 , 1.4 hz , 2h , c2o2c - o - ph ) , 7.81 ( dd , j = 8.5 , 1.4 hz , 2h , c3nhco - o - ph ) , 
 7.63 ( tt , j = 7.4 , 1.3 hz , 1h , c2o2c - p - ph ) , 7.54 ( t , j = 7.9 hz , 2h , c2o2c - m - ph ) , 7.48 ( tt , j = 7.4 , 
 1.9 hz , 1h , c3nhco - p - ph ) , 7.437.34 
 ( m , 6h , c3-o - ph , c3-m - ph , and c3nhco - m - ph ) , 7.307.21 
 ( m , 2h , c3-p - ph and c3nh ) , 6.28 ( s , 
 1h , h10 ) , 6.13 ( br dd , j = 9 , 9 hz , 1h , h13 ) , 5.69 
 ( dd , j = 8.5 , 3.9 hz , 1h , h3 ) , 5.66 ( d , j = 7.2 hz , 1h , h2 ) , 5.19 ( d , j = 4.0 hz , 
 1h , h2 ) , 4.96 ( dd , j = 9.6 , 2.1 hz , 1h , h5 ) , 
 4.44 ( ddd , j = 10.8 , 6.4 , 4.3 hz , 1h , h7 ) , 4.31 ( d , j = 8.4 hz , 1h , h20 ) , 4.20 ( d , j = 8.3 hz , 1h , h20 ) , 3.79 ( d , j = 7.0 hz , 1h , 
 h3 ) , 2.56 ( ddd , j = 14.9 , 9.9 , 6.6 hz , 1h , h6 ) , 
 2.45 ( overlapping m , 1h , c7oh and s , 3h , c4oac ) , 2.302.18 
 ( overlapping m , 1h , h14 and s , 3h , c10oac ) , 1.971.84 
 ( m , 8h , h14 , c18h3 , sioac , and h6 ) , 1.67 
 ( s , 3h , c19h3 ) , 1.61 ( s , 1h , c1oh ) , 1.30 ( s , 9h , c2osioc(ch3)2 ] , 1.26 ( s , 9h , 
 c2osioc(ch3)2 ] , 1.22 ( s , 3h , c17h3 ) , and 1.12 ( s , 3h , c16h3 ) . c nmr ( 75 mhz , cdcl3 ) :  
 204.1 , 171.6 , 170.9 , 170.3 , 170.2 , 167.2 , 167.1 , 143.2 , 138.2 , 134.4 , 
 133.9 , 132.7 , 131.8 , 130.4 , 129.4 , 128.92 , 128.85 , 128.7 , 128.1 , 127.4 , 
 127.1 , 84.7 , 81.1 , 79.3 , 76.6 , 75.9 , 75.4 , 75.31 , 75.27 ( 2 ) , 
 72.3 , 71.6 , 58.7 , 56.1 , 45.7 , 43.3 , 35.70 , 35.68 , 31.34 , 31.32 , 26.9 , 
 23.1 , 22.9 , 22.4 , 21.1 , 15.2 , and 9.8 . hrms ( esi ) calcd for c57h71nnao18si [ m + na ] 1108.4333 ; 
 found 1108.4360 . paclitaxel ( 58.0 mg , 0.0679 mmol , 1.0 equiv ) 
 was dissolved in dry thf ( 1.0 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and a stir bar . pyridine ( 25 l , 0.309 
 mmol , 4.5 equiv ) was added by wiretrol . triethoxychlorosilane ( 5a ) ( 50 l , 0.255 mmol , 3.8 equiv ) was added , and a 
 white precipitate was immediately observed . the suspension was allowed 
 to stir for 2 h at room temperature and then diluted with hexanes / etoac 
 ( 1:1 ) . the slurry was filtered through a short plug of celite to remove 
 the pyridinium salt , and the filtrate was concentrated under reduced 
 pressure . the residue was purified by mplc ( sio2 , 2:1 hexanes / etoac ) 
 to yield 2a as a white crystalline solid ( 68.0 mg , 0.058 
 mmol , 85% ) . if necessary , residual etoac was removed by storage under 
 high vacuum for 24 h. h nmr ( 500 mhz , cdcl3 ) :  8.12 ( dd , j = 8.5 , 1.5 hz , 2h , 
 c2o2c - o - ph ) , 7.78 ( dd , j = 8.5 , 1.5 hz , 2h , c3nhco - o - ph ) , 7.62 ( tt , j = 7.5 , 1.0 hz , 1h , c2o2c - p - ph , 1h ) , 7.547.46 ( m , 3h , c2o2c - m - ph and c3nhco - p - ph ) , 7.447.36 ( m , 
 6h , c3-o - ph , c3-m - ph , and c3nhco - m - ph ) , 7.29 ( tt , j = 7.0 , 1.5 hz , 1h , c3-p - ph ) , 
 7.20 ( d , j = 8.5 hz , 1h , c3nh ) , 6.58 ( s , 
 1h , h10 ) , 6.18 ( br dd , j = 9 , 9 hz , 1h , h13 ) , 5.72 
 ( dd , j = 8.5 , 3.0 hz , 1h , h3 ) , 5.71 ( d , j = 6.5 hz , 1h , h2 ) , 4.98 ( d , j = 3.0 hz , 
 1h , 2h ) , 4.96 ( dd , j = 10.0 , 2.0 hz , 1h , 
 h5 ) , 4.62 ( dd , j = 10.5 , 6.7 hz , 1h , h7 ) , 4.31 ( d , j = 8.5 hz , 1h , h20 ) , 4.20 ( d , j = 8.5 hz , 1h , h20 ) , 3.85 ( d , j = 7.0 hz , 1h , 
 h3 ) , 3.76 [ q , j = 7.0 hz , 6h , c7osi(och2ch3)3 ] , 3.71 [ q , j = 7.0 hz , 6h , c2osi(och2ch3)3 ] , 2.66 ( ddd , j = 14.5 , 9.5 , 6.5 hz , 1h , h6 ) , 2.45 ( s , 3h , c4oac ) , 
 2.33 ( dd , j = 15.4 , 9.4 hz , 1h , h14 ) , 2.15 
 ( s , 3h , c10oac ) , 2.08 ( d , j = 1.5 hz , 3h , c18h3 ) , 2.07 ( dd , j = 15.1 , 9.0 hz , 1h , h14 ) , 
 1.96 ( ddd , j = 14.5 , 10.8 , 2.2 hz , 1h , h6 ) , 
 1.73 ( s , 3h , c19h3 ) , 1.65 ( br s , 1h , c1oh ) , 1.23 ( s , 3h , 
 c17h3 ) , 1.19 [ t , j = 7.0 hz , 9h , c7osi(och2ch3)3 ] , 1.17 ( s , 3h , c16h3 ) , and 1.15 [ t , j = 7.0 hz , 9h , c2osi(och2ch3)3 ] . c nmr ( 75 mhz , 
 cdcl3 ) :  202.6 , 171.0 , 169.8 , 169.0 , 167.3 , 167.2 , 
 141.0 , 138.2 , 134.3 , 133.9 , 133.3 , 132.0 , 130.4 , 129.4 , 128.9 , 128.8 , 
 128.7 , 128.1 , 127.3 , 126.8 , 84.5 , 81.2 , 78.9 , 76.7 , 75.9 , 75.02 , 74.99 , 
 72.1 , 71.6 , 59.7 , 59.5 , 58.3 , 55.5 , 46.9 , 43.4 , 36.5 , 35.5 , 26.7 , 
 23.0 , 21.4 , 21.0 , 18.0 ( 2 ) , 14.2 , and 10.4 . hrms ( esi ) calcd 
 for c59h79nnao20si2 [ m 
 + na ] 1200.4626 , found 1200.4631 . ir ( thin film ) 3500 
 ( br ) , 2976 , 2928 , 2896 , 1744 , 1725 , 1644 , 1603 , 1580 , 1541 , 1486 , 
 1451 , 1370 , 1314 , 1268 , 1238 , 1169 , 1098 , 1080 , 1027 , 969 , 891 , 842 , 
 795 , and 708 cm . tlc rf ( 2:1 hexanes / etoac ) = 0.4 . paclitaxel ( 57.8 mg , 0.0677 mmol , 1.0 equiv ) 
 was dissolved in dry thf ( 1.5 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . pyridine ( 25 l , 
 0.309 mmol , 4.6 equiv ) was added by wiretrol . a 1.67:1 mixture of 
 tri - n - octyloxychlorosilane ( 5b)/tetra - n - octyloxysilane ( 0.155 
 mg , 0.199 mmol , 2.9 equiv of tri - n - octyloxychlorosilane ) 
 was added , and formation of a white precipitate was immediately observed . the culture tube was capped , and the suspension was allowed to stir 
 for 5 h at room temperature . the reaction mixture was diluted with 
 a mixture of hexanes / etoac ( 1:1 ) , and the slurry was filtered through 
 a short plug of celite to remove the pyridinium salt . the filtrate 
 was concentrated under reduced pressure , and the residue was purified 
 by mplc ( sio2 , 9:1 hexanes / etoac ) to yield 2b as a colorless viscous glass ( 88.1 mg , 0.0523 mmol , 77.3% ) . additional 
 elution with hexanes / etoac ( 2:1 ) yielded 1b ( 1.7 mg , 
 0.0013 mmol , 2.0% ) . h nmr ( 500 mhz , cdcl3 ) : 
  8.13 ( dd , j = 8.6 , 1.4 hz , 2h , c2o2c - o - ph ) , 7.78 ( dd , j = 8.6 , 1.5 
 hz , 2h , c3nhco - o - ph ) , 7.60 ( tt , j 
 = 7.4 , 1.2 hz , 1h , c2o2c - p - ph , 
 1h ) , 7.547.46 ( m , 3h , c2o2c - m - ph 
 and c3nhco - p - ph ) , 7.447.35 ( m , 6h , 
 c3-o - ph , c3-m - ph , 
 and c3nhco - m - ph ) , 7.28 ( tt , j = 7.2 , 1.3 hz , 1h , c3-p - ph ) , 7.22 ( d , j = 8.7 hz , 1h , c3nh ) , 6.55 ( s , 1h , h10 ) , 6.23 ( br 
 dd , j = 10 , 9 hz , 1h , h13 ) , 5.74 ( dd , j = 8.6 , 3.0 hz , 1h , h3 ) , 5.70 ( d , j = 7.1 
 hz , 1h , h2 ) , 4.99 ( d , j = 3.0 hz , 1h , 2h ) , 
 4.94 ( dd , j = 9.7 , 1.9 hz , 1h , h5 ) , 4.61 ( dd , j = 10.6 , 6.8 hz , 1h , h7 ) , 4.31 ( d , j = 8.4 hz , 1h , h20 ) , 4.20 ( d , j = 8.4 hz , 1h , 
 h20 ) , 3.86 ( d , j = 7.0 hz , 1h , h3 ) , 3.67 { t , j = 6.7 hz , 6h , c7osi[och2(ch2)6ch3]3 } , 3.61 
 { t , j = 6.7 hz , 6h , c2osi[och2(ch2)6ch3]3 } , 2.65 ( ddd , j = 14.7 , 9.7 , 6.8 hz , 
 1h , h6 ) , 2.45 ( s , 3h , c4oac ) , 2.33 ( dd , j = 15.3 , 9.4 hz , 1h , h14 ) 2.13 ( s , 3h , c10oac ) , 2.06 ( d , j = 1.2 hz , 3h , c18h3 ) , 2.092.02 ( m , 
 1h , h14 ) , 1.96 ( ddd , j = 14.5 , 10.8 , 2.2 hz , 
 1h , h6 ) , 1.73 ( s , 3h , c19h3 ) , 1.66 ( br s , 1h , c1oh ) , 
 1.561.44 { m , 12h , c2osi[och2ch2(ch2)5ch3]3 and c7osi[och2ch2(ch2)5ch3]3 } , 1.341.21 { m , 63h , c17h3 , c2osi[och2ch2(ch2)5ch3]3 , and c7osi[och2ch2(ch2)5ch3]3 } , 1.17 ( s , 3h , c16h3 ) , and 0.88 { overlapping t s , j = 6.8 hz , 
 18h , c2osi[och2ch2(ch2)5ch3]3 and c7osi[och2ch2(ch2)5ch3]3}. c nmr ( 75 mhz , cdcl3 ) :  202.4 , 170.9 , 169.8 , 
 168.7 , 167.3 , 167.2 , 140.9 , 138.3 , 134.3 , 133.8 , 133.3 , 131.9 , 130.4 , 
 129.4 , 128.91 , 128.89 , 128.8 , 128.1 , 127.3 , 126.8 , 84.6 , 81.2 , 79.0 , 
 76.8 , 75.8 , 75.1 , 74.9 , 72.0 , 71.5 , 64.1 , 63.9 , 58.3 , 55.5 , 46.8 , 
 43.5 , 36.6 , 35.6 , 32.5 , 32.4 , 32.1 , 32.0 , 29.6 , 29.63 , 29.60 , 29.57 , 
 26.7 , 25.92 , 25.89 , 23.0 , 22.91 , 22.90 , 21.6 , 21.1 , 14.3 ( 2 ) , 
 14.1 , and 10.4 . hrms ( esi ) calcd for c95h151nnao20si2 [ m + na ] 1705.0260 ; found 
 1705.0228 . ir ( thin film ) 3500 ( br ) , 2927 , 2856 , 1741 , 1728 , 1634 , 
 1580 , 1545 , 1456 , 1371 , 1315 , 1270 , 1239 , 1174 , 1095 , 1028 , 989 , 968 , 
 924 , 893 , 843 , 779 , and 709 cm . paclitaxel ( 30.1 mg , 0.0352 mmol , 1.0 equiv ) 
 was dissolved in dry thf ( 1.0 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . pyridine ( 15 l , 
 0.185 mmol , 5.3 equiv ) was added by wiretrol . a 3.5:1 mixture of triisopropoxychlorosilane 
 ( 5c)/tetraisopropoxysilane 
 ( 0.0424 mg , 0.134 mmol , 2.9 equiv of triisopropoxychlorosilane ) was 
 added . the culture tube was capped , and a white precipitate was observed 
 within minutes . the suspension was stirred at room temperature for 
 18 h , and the mixture was filtered through a short plug of celite 
 to remove the triethylammonium salt . the filtrate was concentrated 
 under reduced pressure , and the residue was redissolved in a mixture 
 of hexanes / etoac ( 2:1 ) . purification by mplc ( sio2 , 2:1 
 hexanes / ethyl acetate ) yielded the title compound as a white , crystalline 
 solid ( 29.8 mg , 0.0236 mmol , 67.0% ) . h nmr ( 500 mhz , cdcl3 ) :  8.12 ( dd , j = 8.5 , 1.5 hz , 2h , 
 c2o2c - o - ph ) , 7.80 ( dd , j = 8.4 , 1.5 hz , 2h , c3nhco - o - ph ) , 7.62 ( tt , j = 7.4 , 1.7 hz , 1h , c2o2c - p - ph , 1h ) , 7.557.46 ( m , 3h , c2o2c - m - ph and c3nhco - p - ph ) , 7.437.34 ( m , 
 6h , c3-o - ph , c3-m - ph , and c3nhco - m - ph ) , 7.297.24 
 ( m , 1h , c3-p - ph ) , 7.17 ( d , j = 8.4 hz , 1h , c3nh ) , 6.53 ( s , 1h , h10 ) , 6.14 ( br dd , j = 9 , 9 hz , 1h , h13 ) , 5.70 ( d , j = 7.3 
 hz , 1h , h2 ) , 5.67 ( dd , j = 8.4 , 3.6 hz , 1h , h3 ) , 
 5.00 ( d , j = 3.6 hz , 1h , h2 ) , 4.96 ( dd , j = 9.4 , 2.0 hz , 1h , h5 ) , 4.61 ( dd , j = 10.7 , 6.7 , hz , 1h , h7 ) , 4.31 ( d , j = 8.8 hz , 1h , 
 h20 ) , 4.19 ( d , j = 8.6 hz , 1h , h20 ) , 
 4.13 and 4.12 { overlapping septs , j = 6.2 hz , 6h , 
 c2osi[och(ch3)2]3 and c7osi[och(ch3)2]3 } , 3.85 ( d , j = 7.4 hz , 1h , h3 ) , 2.68 
 ( ddd , j = 14.7 , 9.7 , 6.8 hz , 1h , h6 ) , 2.41 
 ( s , 3h , c4oac ) , 2.30 ( dd , j = 15.1 , 9.3 hz , 1h , h14 ) , 
 2.14 ( s , 3h , c10oac ) , 2.10 ( d , j = 1.2 hz , 3h , c18h3 ) , 2.03 ( dd , j = 15.7 , 9.5 hz , 1h , h14 ) , 
 1.95 ( ddd , j = 14.6 , 10.9 , 2.2 hz , 1h , h6 ) , 
 1.72 ( s , 3h , c19h3 ) , 1.61 ( br s , 1h , c1oh ) , 1.23 ( m , 3h , 
 c17h3 ) , and 1.181.10 { m , 39h , c2osi[och(ch3)a(ch3)b]3 } , c2osi[och(ch3)a(ch3)b]3 , c7osi[och(ch3)a(ch3)b]3 } , c7osi[och(ch3)a(ch3)b]3 , and c16h3}. c nmr ( 125 mhz , cdcl3 ) :  202.6 , 171.1 , 169.6 , 168.9 , 167.3 , 167.2 , 141.2 , 138.4 , 
 134.4 , 133.8 , 133.3 , 131.9 , 130.4 , 129.5 , 128.9 ( 2 ) , 128.8 , 
 128.1 , 127.3 , 127.0 , 84.6 , 81.2 , 80.0 , 76.8 , 75.9 , 75.2 , 74.9 , 72.3 , 
 71.7 , 66.6 , 66.2 , 58.3 , 55.9 , 46.8 , 43.5 , 36.7 , 35.5 , 26.8 , 25.5 , 
 25.42 , 25.41 , 25.38 , 23.0 , 21.5 , 21.1 , 14.7 , and 10.5 . hrms ( esi ) 
 calcd for c65h91nnao20si2 [ m + na ] 1284.5565 , found 1284.5563 . ir ( thin film ) 
 3500 ( br ) , 2973 , 2933 , 1725 , 1671 , 1603 , 1582 , 1512 , 1484 , 1452 , 1371 , 
 1313 , 1267 , 1238 , 1173 , 1116 , 1047 , 989 , 893 , 839 , 767 , and 711 . bis(triethoxy)silicate ester 2a ( 99.5 mg , 
 0.0845 mmol , 1.0 equiv ) was dissolved in acetone - d6 ( 1.8 ml , dried over 3  molecular sieves ) in an 
 nmr sample tube . a 9:1 mixture of d2o / tfa was added ( 200 
 l ) , and the reaction progress was monitored by h nmr spectroscopy . after 8 min at 21.4 c , the mixture was 
 transferred into saturated aqueous nahco3 ( 2 ml ) . the combined organic extracts were dried over mgso4 , filtered , and concentrated under reduced pressure . the residue 
 was purified by mplc ( sio2 , 2:1 hexanes / etoac ) to provide 
 recovered starting material 2a ( 27.3 mg , 0.0232 mmol , 
 27.4% ) . additional elution in 1:1 hexanes / etoac gave the title compound 
 as a white , crystalline solid [ 56.9 mg , 0.0560 mmol , 66.3% ( 91.4% 
 brsm ) ] . h nmr ( 500 mhz , cdcl3 ) :  8.12 
 ( dd , j = 8.5 , 1.3 hz , 2h , c2o2c - o - ph ) , 7.75 ( dd , j = 8.5 , 1.4 hz , 2h , c3nhco - o - ph ) , 7.61 ( tt , j = 7.5 , 1.2 hz , 1h , c2o2c - p - ph , 1h ) , 7.537.46 ( m , 5h , c2o2c - m - ph , c3nhco - p - ph , and c3-o - ph , ) , 7.437.37 ( m , 
 4h , c3-m - ph and c3nhco - m - ph ) , 7.34 ( tt , j = 7.3 , 1.2 hz , 1h , c3-p - ph ) , 7.09 ( d , j = 9.0 hz , 1h , c3nh ) , 
 6.56 ( s , 1h , h10 ) , 6.18 ( br dd , j = 9 , 9 hz , 1h , 
 h13 ) , 5.80 ( dd , j = 6.9 , 2.5 hz , 1h , h3 ) , 
 5.69 ( d , j = 6.9 hz , 1h , h2 ) , 4.93 ( dd , j 
 = 9.6 , 1.7 hz , 1h , h5 ) , 4.78 ( dd , j = 4.9 , 
 2.7 hz , 1h , 2h ) , 4.57 ( dd , j = 10.5 , 6.9 
 hz , 1h , h7 ) , 4.30 ( d , j = 8.4 hz , 1h , h20 ) , 
 4.19 ( dd , j = 8.3 , 0.9 hz , 1h , h20 ) , 3.83 
 ( d , j = 6.9 hz , 1h , h3 ) , 3.76 [ q , j = 7.0 hz , 6h , c7osi(och2ch3)3 ] , 3.69 ( br s , 1h , c2oh ) , 2.65 
 ( ddd , j = 14.7 , 9.7 , 6.9 hz , 1h , h6 ) , 2.37 
 ( s , 3h , c4oac ) , 2.352.25 ( m , 2h , h14 and h14 ) , 
 2.15 ( s , 3h , c10oac ) , 1.95 ( ddd , j = 14.6 , 10.7 , 2.1 
 hz , 1h , h6 ) , 1.93 ( d , j = 1.3 hz , 3h , c18h3 ) , 1.76 ( br s , 1h , c1oh ) , 1.73 ( s , 3h , c19h3 ) , 
 1.23 ( s , 3h , c17h3 ) , 1.19 [ t , j = 7.0 
 hz , 9h , c7osi(och2ch3)3 ] , and 1.16 ( s , 3h , c16h3 ) . c nmr ( 125 mhz , cdcl3 ) :  202.4 , 172.6 , 170.4 , 169.0 , 
 167.2 , 167.1 , 140.1 , 138.2 , 133.9 , 133.8 , 132.1 , 130.3 , 129.4 , 129.1 , 
 128.89 , 128.87 , 128.5 , 127.3 , 127.24 , 127.23 , 84.4 , 81.5 , 78.8 , 76.8 , 
 76.1 , 74.8 , 73.4 , 72.5 , 72.1 , 59.5 , 58.6 , 55.0 , 47.0 , 43.4 , 36.7 , 
 35.6 , 26.8 , 22.9 , 21.1 , 21.0 , 18.2 , 14.5 , and 10.3 . hrms ( esi ) calcd 
 for c53h65nnao17si [ m + na ] 1038.3914 , found 1038.3914 . ir ( thin film ) 3500 ( br ) , 2975 , 2898 , 
 1724 , 1653 , 1602 , 1580 , 1515 , 1485 , 1451 , 1394 , 1370 , 1314 , 1266 , 
 1240 , 1172 , 1079 , 1025 , 969 , 913 , 888 , 839 , 797 , and 712 cm . bis(trioctyloxy)silicate ester 2b ( 88.1 mg , 0.0523 mmol , 1.0 equiv ) was dissolved in acetone - d6 ( 1.8 ml , dried over 3  molecular sieves ) 
 in an nmr tube . a 9:1 mixture of d2o / tfa was added ( 200 
 l ) , and the solution became white and cloudy . after 30 min at room temperature , the solution was transferred into 
 saturated aqueous nahco3 ( 2 ml ) . this mixture was extracted 
 with ch2cl2 ( 3  5 ml ) . the combined organic 
 layers were dried over mgso4 and concentrated under reduced 
 pressure . the residue was purified by mplc ( sio2 , 3:1 hexanes / etoac ) 
 to provide recovered 2b ( 12.9 mg , 0.0076 mmol , 27.4% ) . additional elution in 2:1 hexanes / etoac gave the title compound as 
 a crystalline solid [ 37.3 mg , 0.0294 mmol , 56.2% ( 65.7% brsm ) ] . h nmr ( 500 mhz , cdcl3 ) :  8.12 ( dd , j = 8.5 , 1.3 hz , 2h , c2o2c - o - ph ) , 7.75 ( dd , j = 8.5 , 1.4 hz , 2h , c3nhco - o - ph ) , 7.61 ( tt , j = 7.4 , 1.3 hz , 1h , c2o2c - p - ph , 1h ) , 7.537.47 ( m , 5h , c2o2c - m - ph , c3nhco - p - ph , and c3-o - ph , ) , 7.437.38 ( m , 
 4h , c3-m - ph and c3nhco - m - ph ) , 7.34 ( tt , j = 7.2 , 1.3 hz , 1h , c3-p - ph ) , 7.06 ( d , j = 9.0 hz , 1h , c3nh ) , 
 6.53 ( s , 1h , h10 ) , 6.17 ( br dd , j = 9 , 9 hz , 1h , 
 h13 ) , 5.81 ( dd , j = 6.8 , 2.4 hz , 1h , h3 ) , 
 5.68 ( d , j = 6.9 hz , 1h , h2 ) , 4.92 ( dd , j 
 = 9.6 , 1.8 hz , 1h , h5 ) , 4.78 ( dd , j = 4.8 , 
 2.6 hz , 1h , 2h ) , 4.56 ( dd , j = 10.5 , 6.7 
 hz , 1h , h7 ) , 4.29 ( d , j = 8.3 hz , 1h , h20 ) , 
 4.19 ( d , j = 8.5 hz , 1h , h20 ) , 3.83 ( d , j = 7.0 hz , 1h , h3 ) , 3.66 { t , j = 6.7 hz , 
 6h , c7osi[och2(ch2)6ch3]3 } , 3.60 ( d , j = 4.9 hz , 1h , c2oh ) , 2.64 ( ddd , j = 14.7 , 9.7 , 6.9 hz , 1h , h6 ) , 2.37 ( s , 3h , c4oac ) , 2.342.27 
 ( m , 2h , h14 and h14 ) , 2.14 ( s , 3h , c10oac ) , 1.971.90 
 ( m , 4h , h6 and c18h3 ) , 1.741.70 ( m , 4h , 
 c1oh and c19h3 ) , 1.52 { tt , j = 6.8 , 6.8 
 hz , 6h , c7osi[och2ch2(ch2)5ch3]3 } , 1.341.22 
 { m , 33h , c17h3 and c7osi[och2ch2(ch2)5ch3]3 } , 1.16 ( s , 3h , c16h3 ) , and 0.88 { t , j = 6.8 hz , 9h , c7osi[och2ch2(ch2)5ch3]3}. c nmr ( 125 mhz , cdcl3 ) :  
 202.2 , 172.7 , 170.3 , 168.8 , 167.2 , 167.0 , 140.0 , 138.3 , 133.93 , 133.89 , 
 132.1 , 130.4 , 129.4 , 129.1 , 128.9 ( x3 ) , 128.5 , 127.3 , 127.2 , 84.5 , 
 81.5 , 78.8 , 76.8 , 76.0 , 74.9 , 72.5 , 72.3 , 71.7 , 63.9 , 58.6 , 54.9 , 
 47.0 , 43.4 , 36.6 , 35.6 , 32.5 , 32.1 , 29.62 , 29.57 , 26.8 , 25.9 , 22.91 , 
 22.88 , 21.1 , 21.0 , 14.5 , 14.3 , and 10.3 . hrms ( esi ) calcd for c71h101nnao17si [ m + na ] 1290.6731 ; 
 found 1290.6738 . ir ( thin film ) 3500 ( br ) , 2926 , 2855 , 1732 , 1710 , 
 1673 , 1602 , 1582 , 1452 , 1396 , 1370 , 1317 , 1281 , 1269 , 1241 , 1179 , 
 1093 , 1025 , 988 , 968 , 890 , 844 , 809 , and 712 cm . bis - silicate ester 2b ( 102.3 
 mg , 0.081 mmol , 1.0 equiv ) was dissolved in acetone - d6 ( 1.35 ml , dried over 3  molecular sieves ) . a 9:1 
 mixture of d2o / tfa was added ( 150 l ) , and the solution 
 became white and cloudy . upon being shaken for 30 s , after 18 h at room temperature , 
 the solution was transferred into saturated aqueous nahco3 ( 3 ml ) . the residue was purified by mplc ( sio2 , 1:1 hexanes / etoac ) to provide recovered 2c ( 35.8 
 mg , 0.028 mmol , 35% ) and the title compound as a crystalline solid 
 [ 43.3 mg , 0.041 mmol , 50.5% ( 77% brsm ) ] . h nmr ( 500 mhz , 
 cdcl3 ) :  8.13 ( dd , j = 8.4 , 1.3 
 hz , 2h , c2o2c - o - ph ) , 7.75 ( dd , j = 8.5 , 1.3 hz , 2h , c3nhco - o - ph ) , 
 7.62 ( tt , j = 7.0 , 1.3 hz , 1h , c2o2c - p - ph , 1h ) , 7.537.49 ( m , 5h , c2o2c - m - ph , c3nhco - p - ph , and c3-o - ph , ) , 7.437.39 ( m , 4h , c3-m - ph and c3nhco - m - ph ) , 7.34 ( tt , j = 7.3 , 1.2 hz , 1h , c3-p - ph ) , 
 7.05 ( d , j = 9.0 hz , 1h , c3nh ) , 6.50 ( s , 
 1h , h10 ) , 6.19 ( ddq , j = 9.1 , 9.1 , 1.4 hz , 1h , h13 ) , 
 5.80 ( dd , j = 9.0 , 2.4 hz , 1h , h3 ) , 5.68 
 ( d , j = 7.0 hz , 1h , h2 ) , 4.94 ( dd , j = 9.6 , 1.9 hz , 1h , h5 ) , 4.81 ( d , j = 2.6 hz , 1h , 
 h2 ) , 4.57 ( dd , j = 6.8 , 10.5 hz , 1h , h7 ) , 
 4.30 ( d , j = 8.4 hz , 1h , h20 ) , 4.19 ( d , j = 8.5 hz , 1h , h20 ) , 4.11 { sept , j = 6.1 hz , 3h , c7osi[och(ch3)2]3 } , 3.83 ( d , j = 7.0 hz , 1h , h3 ) , 3.60 
 ( br s , 1h , c2oh ) , 2.67 ( ddd , j = 14.8 , 9.8 , 
 6.9 hz , 1h , h6 ) , 2.37 ( s , 3h , c4oac ) , 2.362.25 ( m , 
 2h , h14 and h14 ) , 2.14 ( s , 3h , c10oac ) , 1.96 ( d , j = 1.5 hz , c18h3 ) , 1.951.91 ( ddd , j 14.7 , 10.6 , 2.1 hz , 1h , h6 ) , 1.73 ( s , 3h , c19h3 ) , 1.65 ( br s , 1h , c1oh ) , 1.24 ( s , c17h3 ) , 1.160 
 ( s , 3h , c16h3 ) , 1.160 , { d , j = 6.1 , 9h , 
 c7osi[och(ch3)3 ] } , and 1.15 { d , j = 6.1 hz , 9h 
 c7osi[och(ch3)3]}. c nmr ( 125 mhz , cdcl3 ) :  202.5 , 172.7 , 170.3 , 168.9 , 167.2 , 167.1 , 140.3 , 
 138.2 , 133.92 , 133.80 , 132.1 , 130.4 , 129.4 , 129.2 ( 2x ) , 128.9 ( 2 ) , 
 128.5 , 127.3 , 127.2 , 84.5 , 81.5 , 78.8 , 76.8 , 76.0 , 74.9 , 73.3 , 72.6 , 
 72.4 , 66.3 { sioch(ch3)2 } , 58.5 , 
 54.9 , 47.0 , 43.4 , 36.8 , 35.6 , 26.9 , 25.5 { sioch(ch3)2 } , 25.4 { sioch(ch3)2 } , 22.9 , 21.1 , 21.0 , 14.8 , and 10.4 . hrms ( esi ) 
 calcd for c56h71nnao17si [ m + na ] 1080.4383 ; found 1080.4393 . ir ( thin film ) ( br ) 3448 , 3067 , 
 3026 , 2972 , 2934 , 2898 , 1724 , 1662 , 1602 , 1581 , 1485 , 1452 , 1370 , 
 1315 , 1289 , 1269 , 1239 , 1174 , 1136 , 1113 , 1048 , 987 , 969 , 949 , 892 , 
 838 , 803 , and 775 cm . docetaxel 
 ( 75.0 mg , 0.0930 mmol , 1.0 equiv ) was 
 dissolved in dry thf ( 2.0 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . n , n - dimethylbutylamine ( 35 l , 0.250 mmol , 2.7 equiv ) 
 was added by wiretrol . triethoxychlorosilane ( 5a ) ( 50 
 l , 50.6 mg , 0.255 mmol , 2.7 equiv ) was added . the culture tube 
 was sealed , and the suspension was allowed to stir for 2 h at room 
 temperature . a white precipitate was observed immediately upon the 
 addition of the chlorosilane to the reaction mixture . the thf was 
 removed by evaporation under reduced pressure , and the solid residue 
 was triturated with a mixture of hexanes / etoac ( 1:1 ) , and the resulting 
 slurry was filtered through a short plug of celite to remove the ammonium 
 salt . the filtrate was concentrated under reduced pressure , and the 
 residue was purified by mplc ( sio2 , 1:1 hexanes / etoac ) 
 to yield the title compound as a white , crystalline solid ( 58.1 mg , 
 0.060 mmol , 64.5% ) . h nmr ( 500 mhz , cdcl3 , 
 some resonances were broadened presumably because of the presence 
 of nboc rotamers ) :  8.10 ( d , j = 7.9 hz 2h , 
 o2c - o - ph ) , 7.60 ( t , j = 7.2 hz , 1h , o2c - p - ph ) , 7.50 ( t , j = 7.9 hz , 2h , o2c - m - ph ) , 7.36 
 ( t , 2h , j = 8.0 hz , c3-m - ph ) , 7.33 ( d , 2h , j = 7.2 hz , c3-o - ph ) , 7.25 ( t , j = 6.5 hz 1h , c3-p - ph ) , 6.27 ( br m , 1h , h13 ) , 5.67 ( d , j = 7.3 hz , 1h , h2 ) , 5.62 ( d , j = 8.9 hz , 1h , h3 ) , 
 5.28 ( br s , 1h , nh ) , 5.21 ( s , 1h , h10 ) , 4.96 ( dd , j = 9.9 , 1.9 hz , 1h , h5 ) , 4.81 ( br s , 1h , h2 ) , 4.31 ( d , j = 8.6 hz , 1h , h20 ) , 4.25 ( br dd , j = 11.6 , 7.2 , hz , 1h , h7 ) , 4.22 ( d , j = 1.5 hz , 1h , 
 c10oh ) , 4.19 ( d , j = 8.6 hz 1h , 
 h20 ) , 3.92 ( d , j = 6.9 hz , 1h , h3 ) , 3.66 { br 
 q , j = 6.7 , 5.8 hz , 6h , c2osi[och2ch3]3 } , 2.58 ( ddd , j = 14.0 , 9.9 , 6.4 hz , 1h ,  ) , 2.44 ( s , 3h , c4oac ) , 
 2.29 ( br m , 1h , 14 ) , 2.11 ( br m , 1h , 1 ) , 1.93 ( s , 3h , 
 = cch3 ) , 1.85 ( ddd , j = 14.6 , 11.5 , 
 2.8 hz 1h ,  ) , 1.74 ( s , 3h , o = ccch3 ) , 1.71 ( s , 1h , c1oh ) , 1.32 ( br s , 9h , tboc ) , 1.25 { s , c(me)c16h3 } , 
 1.12 [ t , j = 7.0 hz , 9h , c2osi(och2ch3)3 ] , and 1.11 ( s , 3h , c(me)c17h3 ) . c nmr ( 125 mhz , cdcl3 ) :  211.6 ( c9 ) , 170.7 ( c1 ) , 170.0 ( c21 ) , 167.1 ( c2ocobz ) , 155.4 ( c3-nhco ) , 139.3 ( c3-ipso - ph ) , 138.6 ( c12 ) , 135.4 ( c11 ) , 133.7 ( obz - p ) , 130.2 ( obz - i ) , 129.2 ( obz - o ) , 
 128.7 ( obz - m ) , 128.5 ( 2  c3-o - ph ) , 127.6 ( c3-m - ph ) , 126.5 ( c3-p - ph ) , 84.2 ( c5 ) , 80.9 ( ocme3 ) , 79.9 ( c1 ) , 79.0 ( c4 ) , 76.6 ( c20 ) , 75.2 ( c2 ) , 75.0 ( c10 ) , 74.5 
 ( c2 ) , 71.9 ( c13 ) , 71.2 ( c7 ) , 59.4 ( 3x c2osioch2ch3 ) , 57.5 ( c8 ) , 56.3 ( c3 ) , 
 46.4 ( c3 ) , 43.1 ( c15 ) , 36.9 ( c6 ) , 35.6 ( c14 ) , 28.2 [ c3-nhcoc(ch3 ) ] , 26.4 ( c16 ) , 22.7 ( c22 ) , 21.0 ( c17 ) , 18.0 
 ( sioch2ch3 ) , 14.1 ( c18 ) , and 
 9.9 ( c19 ) . hrms ( esi ) calcd for c49h67nnao17si [ m + na ] 992.4070 ; found 992.4083 . ir ( thin 
 film ) 3443 , 2977 , 2930 , 2897 , 2368 , 1756 , 1712 , 1495 , 1453 , 1392 , 
 1367 , 1314 , 1271 , 1244 , 1166 , 1105 , 1081 , 1025 , 983 , 915 , 88 , 798 , 
 786 , and 758 cm . docetaxel ( 36.4 mg , 0.0450 mmol , 1.0 equiv ) 
 was dissolved in dry thf ( 2.0 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . n , n - dimethylbutylamine ( 35 l , 0.250 mmol , 5.5 equiv ) 
 was added by wiretrol . tri - n - octyloxychlorosilane 
 ( 5b ) ( containing 20% 
 of tetra - n - octyloxysilane ; 50 l , estimated 
 to contain 32.0 mg , 0.071 mmol , 1.6 equiv of the tri - n - octyloxychlorosilane ) was added . the culture tube was sealed , and 
 the suspension was allowed to stir for 3 h at room temperature . a 
 white precipitate was observed to grow over the first 30 min of the 
 reaction period . the solid residue was triturated with a mixture of hexanes / etoac 
 ( 2:1 ) , and the resulting slurry was filtered through a short plug 
 of celite to remove the ammonium salt . the filtrate was concentrated 
 under reduced pressure , and the residue was purified by mplc ( sio2 , 2:1 hexanes / etoac ) to yield the title compound as a white , 
 crystalline solid ( 35.1 mg , 0.0287 mmol , 63.7% ) . h nmr 
 ( 500 mhz , cdcl3 , some resonances were broadened presumably 
 because of the presence of nboc rotamers ) :  8.12 ( d , j = 7.9 hz 2h , o2c - o - ph ) , 7.60 
 ( t , j = 7.3 hz , 1h , o2c - p - ph ) , 7.50 ( t , j = 7.8 hz , 2h , o2c - m- ph ) , 7.35 ( t , 2h , j = 7.9 hz , c3-m - ph ) , 7.32 ( d , 2h , j = 6.9 hz , c3-o - ph ) , 7.25 ( t , j = 6.8 hz 1h , c3-p - ph ) , 6.28 ( br dd , j = 9 , 9 hz , 1h , h13 ) , 
 5.69 ( d , j = 7.1 hz , 1h , h2 ) , 5.62 ( d , j 
 = 9 hz h3 ) , 5.28 ( br s , 1h , nh ) , 5.20 ( s , 1h , h10 ) , 
 4.96 ( dd , j = 9.6 , 1.8 hz , 1h , h5 ) , 4.81 ( br s , 1h , 
 h2 ) , 4.32 ( d , j = 8.5 hz , 1h , h20 ) , 
 4.25 ( br dd , j = 10.2 , 7.0 , hz , 1h , h7 ) , 4.20 ( d , j = 8.1 hz , 1h , h20 ) , 4.19 ( br s , 1h , c10oh ) , 3.93 
 ( d , j = 7.1 hz , 1h , h3 ) , 3.56 { t , j = 6.5 hz , 6h , c2osi[och2 ( ch2)6ch3]3 } , 2.59 ( ddd , j = 15.8 , 9.5 , 6.5 hz , 1h , h6 ) , 2.43 ( s , 3h , c4oac ) , 
 2.29 ( br m , 1h , h14 ) , 2.12 ( br m , 1h , h14 ) , 1.93 ( s , 
 3h , = cch3 ) , 1.85 ( ddd , j = 13.9 , 
 11.6 , 2.2 hz 1h , h6 ) , 1.75 ( s , 3h , o = ccch3 ) , 1.65 ( d , 1h , j = 2.6 , c1oh ) , 1.46 { br pent , j = 6.4 hz , 6h , c2osi[och2ch2(ch2)5ch3]3 } , 1.32 ( br s , 9h , t - boc ) , 1.311.24 { m , 
 33h , c2osi[och2ch2(ch2)5ch3]3 } , and c(me)c16h3 } , 1.12 ( s , 3h , c(me)c17h3 ) , and 0.89 { t , j = 6.7 hz , 9h , c2osi[och2ch2(ch2)5ch3]3}. c nmr ( 125 mhz , cdcl3 ) :  
 211.9 , 170.8 , 170.1 , 167.3 , 155.3 , 139.6 , 138.9 , 135.5 , 133.8 , 130.4 , 
 129.4 , 128.9 128.7 , 127.8 , 126.7 , 84.4 , 81.1 , 80.0 , 79.2 , 77.6 , 76.8 , 
 75.2 , 74.7 , 72.1 , 71.3 , 64.0 , 57.7 , 56.3 , 46.6 , 43.3 , 37.2 , 35.9 , 
 32.4 , 32.1 , 29.6 , 29.5 , 28.4 , 26.5 , 25.8 , 22.93 , 22.90 , 21.2 , 14.4 , 
 14.3 , and 10.2 . hrms ( esi ) calcd for c67h103nnao17si [ m + na ] 1244.6887 ; found 1244.6954 . ir ( thin film ) 3454 , 3382 , 2926 , 2855 , 1755 , 1737 , 1713 , 1699 , 1495 , 
 1454 , 1367 , 1272 , 1245 , 1165 , 1095 , 1025 , 987 , 946 , 943 , 920 , 888 , 
 865 , 824 , 800 , and 778 cm . docetaxel ( 40.0 mg , 0.0490 mmol , 1.0 equiv ) was 
 dissolved in dry thf ( 2.0 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . n , n - dimethylbutylamine ( 50 l , 0.357 mmol , 7.3 equiv ) 
 was added by wiretrol . triisopropoxychlorosilane ( 5c ) ( containing 80% of triisopropoxychlorosilane ; 
 50 l , estimated to contain 42.0 mg , 0.175 mmol , 3.8 equiv of 
 the triisopropoxychlorosilane ) was added . the culture tube was capped , 
 and the suspension was allowed to stir for 5 h at room temperature . the thf was removed by evaporation under reduced pressure , and the 
 solid residue was triturated with a mixture of hexanes / etoac ( 2.4:1 ) . the resulting slurry was filtered through a short plug of celite to 
 remove the ammonium salt . the filtrate was concentrated under reduced 
 pressure , and the residue was purified by mplc ( sio2 , 2.4:1 
 hexanes / etoac ) to yield the title compound as a white , crystalline 
 solid ( 31.2 mg , 0.0308 mmol , 62.8% ) . h nmr ( 500 mhz , cdcl3 , some resonances were broadened presumably because of the 
 presence of nboc rotamers ) :  8.10 ( d , j = 7.6 
 hz 2h , o2c - o - ph ) , 7.62 ( t , j = 7.4 hz , 1h , o2c - p - ph ) , 7.51 ( t , j = 7.8 hz , 2h , o2c - m - ph ) , 7.35 ( t , 2h , j = 8.0 hz , c3-m - ph ) , 7.32 ( d , 2h , j = 6.9 hz , c3-o - ph ) , 7.23 ( t , j = 6.6 hz 1h , c3-p - ph ) , 6.21 ( br m , 1h , h13 ) , 5.69 ( d , j = 9 hz , 1h , h3 ) , 5.68 ( d , j = 7.0 hz , h2 ) , 
 5.21 ( br s , 1h , nh ) , 5.20 ( s , 1h , h10 ) , 4.96 ( dd , j = 9.6 , 2.1 hz , 1h , h5 ) , 4.81 ( br s , 1h , h2 ) , 4.31 ( d , j = 8.5 hz , 1h , h20 ) , 4.25 ( ddd , j = 11.3 , 8.0 , 7.0 hz , 1h , h7 ) , 4.19 ( br s , 1h , c10oh ) , 4.18 ( d , j = 8.6 hz , 1h , h20 ) , 4.09 { br septet , j 
 = 5.9 hz , 3h , osi[och ( ch3)2]3 } , 3.91 ( d , j = 7.1 hz , 1h , 
 h3 ) , 2.60 ( ddd , j = 14.4 , 9.7 , 6.5 hz , 1h , h6 ) , 
 2.40 ( s , 3h , c4oac ) , 2.22 ( br m , 1h , h14 ) , 2.05 ( br m , 1h , 
 h14 ) , 1.93 ( s , 3h , = cch3 ) , 1.84 ( ddd , j = 14.1 , 11.3 , 2.5 hz 1h , h6 ) , 1.75 ( s , 3h , o = ccc19h3 ) , 1.60 ( br s , 1h , c1oh ) , 1.46 ( d , 1h , j = 
 8.0 hz , c7oh ) , 1.33 ( br s , 9h , t - boc ) , 1.24 [ s , 3h , 
 c(me)c16h3 ] , and 1.141.10 { m , 
 21h , c(me)c17h3 and osi[och(ch3)2]3}. c nmr ( 125 
 mhz , cdcl3 ) :  211.7 , 170.7 , 169.9 , 167.1 , 155.4 , 
 139.5 , 138.7 , 135.2 , 133.7 , 130.2 , 129.2 , 128.7 , 128.5 , 127.6 , 126.6 , 
 84.2 , 80.9 , 79.0 , 76.6 , 75.1 , 75.0 , 74.5 , 73.2 , 71.9 , 71.1 , 66.3 , 
 57.5 , 56.7 , 46.4 , 43.1 , 36.9 , 35.6 , 28.2 , 26.3 , 25.2 , 22.7 , 21.0 , 
 14.4 , and 10.0 . hrms ( esi ) calcd for c52h73nnao17si [ m + na ] 1034.4540 ; found 1034.4545 . ir ( thin 
 film ) 3683 , 2973 , 2917 , 2849 , 2349 , 1757 , 1733 , 1717 , 1701 , 1649 , 
 1631 , 1547 , 1494 , 1461 , 1452 , 1369 , 1271 , 1244 , 1167 , 1114 , 1051 , 
 986 , 892 , 846 , and 778 cm . docetaxel ( 50.5 mg , 0.063 mmol , 1.0 equiv ) was dissolved in dry 
 thf ( 1.0 ml ) in an oven - dried culture tube fitted with a teflon - lined 
 cap and magnetic stir bar . pyridine ( 35 l , 0.45 mmol , 7.2 equiv ) 
 was added by wiretrol . trimenthyloxychlorosilane ( 5d ) ( 50 l , 44 mg , 0.083 mmol , 1.3 equiv ) 
 was added . the culture tube was sealed , and the suspension was allowed 
 to stir for 18 h at 45 c . the solid residue was triturated with a mixture 
 of hexanes / etoac ( 2:1 ) , and the resulting slurry was filtered through 
 a short plug of celite to remove the pyridinium salt . the filtrate 
 was concentrated under reduced pressure , and the residue was purified 
 by mplc ( sio2 , 2.3:1 hexanes / etoac ) to yield the title 
 compound as a white , crystalline solid ( 36.0 mg , 0.028 mmol , 44% ) . h nmr ( 500 mhz , cdcl3 , some resonances were broadened 
 presumably because of the presence of nboc rotamers ) :  8.11 
 ( d , j = 7.5 hz 2h , o2c - o - ph , 7.59 ( t , j = 7.2 hz , 1h , o2c - p - ph ) , 7.49 ( t , j = 7.8 hz , 2h , o2c - m - ph ) , 7.36 ( t , 2h , j = 7.7 hz , 
 c3-m - ph ) , 7.33 ( d , 2h , j = 7.2 hz , c3-o - ph ) , 7.27 ( t , j = 7.0 hz 1h , c3-p - ph ) , 6.23 ( br dd , j = 8.3 , 8.4 hz , 1h , h13 ) , 5.70 ( d , j = 7.1 hz , 1h , h2 ) , 5.50 ( d , j = 9.3 hz , 1h h3 ) , 
 5.24 ( br d , j = 8.8 hz 1h , nh ) , 5.22 ( s , 1h , h10 ) , 
 4.95 ( dd , j = 9.5 , 1.5 hz , 1h , h5 ) , 4.90 ( br s , 1h , 
 h2 ) , 4.31 ( d , j = 8.5 hz , 1h , h20 ) , 
 4.26 ( br dd , j = 11.0 , 7.2 , hz , 1h , h7 ) , 4.21 ( d , j = 7.1 hz , 1h , h20 ) , 4.19 ( br s , 1h , c10oh ) , 3.94 
 ( dd , j = 7.6 , 5.2 hz , 1h , h3 ) , 3.60 ( dt , j = 10.2 , 3.8 hz , 3h , h1menth ) , 2.60 ( ddd , j = 14.5 , 9.7 , 6.6 hz , 1h , h6 ) , 2.39 ( s , 3h , c4oac ) , 
 2.28 ( br m , 1h , h14 ) , 2.21 ( br m , 1h , h14 ) , 2.20 ( dsep , j = 7.0 , 2.1 hz , 3h , h7menth ) , 1.96 ( s , 3h , h18 
 = cch3 ) , 1.85 ( m , 1h , h6 ) , 1.84 ( m , 3h , h6menth ) , 1.75 ( s , 3h , h19 o = ccch3 ) , 1.67 ( s , 
 1h , c1oh ) , 1.58 ( m , 6h , h3menth and h4menth ) , 
 1.33 ( br s , 9h , tboc ) , 1.261.24 [ m , 6h , h5menth and c(me)c16h3 ] , 1.30 [ s , 3h , c(me)c17h3 ] , 1.11 ( m , 3h , h2menth ) , 0.930.86 ( m , 
 6h , h4menth and h6menth ) , 0.88 ( br d , 9h , h8menth ) , 0.87 ( br d , 9h , h9menth ) , 0.79 ( m , 3h , h3menth ) , and 0.73 ( d , j = 6.9 hz , 9h , h10menth ) . c nmr ( 125 mhz , cdcl3 ) :  
 212.1 , 170.8 , 169.9 , 167.3 , 155.7 , 139.9 , 139.1 , 135.3 , 133.8 , 130.4 , 
 129.4 , 128.9 , 128.8 , 127.7 , 126.6 , 84.4 , 81.0 , 79.9 , 79.2 , 76.8 , 75.2 , 
 74.8 , 74.7 , 73.9 , 72.2 , 71.4 ( c1menth ) , 57.7 , 56.5 ( br ) , 
 49.7 ( c2menth ) , 46.5 , 45.0 ( c7menth ) , 43.3 , 
 37.2 , 36.0 , 34.6 ( c5menth ) , 31.7 ( c6menth ) , 
 28.4 , 26.5 , 25.3 ( c3menth ) , 22.82 , 22.78 ( c4menth ) , 22.5 ( c8menth ) , 21.5 ( c9menth ) , 21.3 , 15.8 
 ( c10menth ) , 14.7 , and 10.2 ppm . ( assignments of resonances 
 of the menthyl moieties deduced from c nmr spectrum assignments 
 of [ ( mentho)3sioh ] . hrms ( esi ) 
 calcd for c67h103nnao17si [ m + na ] 1322.7357 ; found 1322.7351 . ir ( thin film ) 3445 , 2953 , 2927 , 
 2872 , 2360 , 2340 , 1762 , 1717 , 1496 , 1454 , 1368 , 1274 , 1245 , 1163 , 
 1108 , 1083 , 1070 , 1052 , 986 , and 889 cm . docetaxel ( 40.0 mg , 0.049 mmol , 1.0 equiv ) 
 was dissolved in dry thf ( 2.0 ml ) in an oven - dried culture tube fitted 
 with a teflon - lined cap and magnetic stir bar . pyridine ( 50 l , 
 0.63 mmol , 12.8 equiv ) was added by wiretrol . dichlorodi - tert - butoxysilane ( 6 ) solution 
 consisting of 90% of the dichlorosilane and 10% of 
 the monochlorosilane ( 100 l , 93 mg , 0.38 mmol , 7.8 equiv ) was 
 added . the culture tube was sealed , and the suspension was allowed 
 to stir for 12 h at 30 c . absolute ethanol dried over 4  
 molecular sieves ( 50 l , 0.85 mmol , 17.5 equiv ) was added , and 
 the reaction mixture continued to stir for another 3 h. the thf was 
 removed by evaporation under reduced pressure . the solid residue was 
 triturated with a mixture of hexanes / etoac ( 2:1 ) , and the resulting 
 slurry was filtered through a short plug of celite to remove the pyridinium 
 salt . the filtrate was concentrated under reduced pressure , and the 
 residue was purified by mplc ( sio2 , 2:1 hexanes / etoac ) 
 to yield the title compound as a white , crystalline solid ( 30.2 mg , 
 0.029 mmol , 60% ) . h nmr ( 500 mhz , cdcl3 , some 
 resonances were broadened presumably because of the presence of nboc 
 rotamers ) :  8.09 ( d , j = 7.6 hz 2h , o2c - o - ph , 7.63 ( t , j = 6.8 
 hz , 1h , o2c - p - ph ) , 7.52 ( t , j 
 = 7.5 hz , 2h , o2c - m - ph ) , 7.43 
 ( t , 2h , j = 8.0 hz , c3-m - ph ) , 7.33 ( br d , 2h , c3-o - ph ) , 7.20 ( br 
 t , 1h , c3-p - ph ) , 6.15 ( br m , 1h , h13 ) , 5.81 
 ( d , j = 7.2 hz , 1h , h2 ) , 5.66 ( d , j = 6.9 hz , 1h h3 ) , 5.18 ( s , 1h , h10 ) , 5.14 ( br s , 1h , nh ) , 
 4.94 ( br dd , j = 9.5 , 2.3 hz , 1h , h5 ) , 4.76 ( br s , 
 1h , h2 ) , 4.30 ( d , j = 8.4 hz , 1h , h20 ) , 
 4.24 ( br dd , j = 10.7 , 6.4 , hz , 1h , h7 ) , 4.18 ( d , 
 1h , j = 9.5 hz , c7oh ) , 4.17 ( d , j = 8.5 hz , 1h , h20 ) , 3.89 ( br d , j = 7 hz , 
 1h , h3 ) , 3.67 [ br q , 2h , c2osi(och2ch3 ) ] , 2.58 ( ddd , j = 14.7 , 9.7 , 6.5 
 hz , 1h , h6 ) , 2.43 ( br d , 1h , c7oh ) , 2.35 ( s , 3h , o = cch3 ) , 2.12 ( br m , 1h , h14 ) , 1.94 ( very 
 br m , 1h , h14 , chemical shift deduced from the cosy spectrum ) , 
 1.91 ( br s , 3h , h18 = cch3 ) , 1.83 ( ddd , j 
 = 13.8 , 11.3 , 2.0 hz , 1h , h6 ) , 1.73 ( s , 3h , h19 o = ccch3 ) , 1.60 ( br s , 2h c7oh and c1oh ) , 1.35 ( br s , 9h , t - boc ) , 1.29 ( br s , 9h , c2osi[oc(ch3 ) ] , 1.26 ( br s , 9h , c2osi[oc(ch3) ] , 1.22 ( s , 3h , c17h3 ) , 1.15 ( br t , j = 6.8 hz , 3h , c2osi[och2ch3 ] ) , and 1.10 ( br s , 3h , c16h3 ) . c nmr ( 125 mhz , cdcl3 ) :  
 211.9 , 170.8 , 170.1 , 167.2 , 155.7 , 139.7 , 139.0 , 135.4 , 133.9 , 130.4 , 
 129.9 , 129.5 , 128.9 , 128.7 , 127.0 , 84.4 , 81.0 , 79.9 , 79.1 , 76.8 , 75.2 , 
 75.1 , 74.7 , 74.0 , 72.1 , 71.0 , 57.7 , 59.3 , 57.4 , 46.5 , 43.2 , 37.1 , 
 35.7 , 31.41 , 31.40 , 28.4 , 26.5 , 22.9 , 21.2 , 18.2 , 14.6 , and 10.2 ppm . hrms ( esi ) calcd for c53h75nnao17si [ m + na ] 1048.4696 ; found 1048.4695 . ir ( thin film ) 
 3456 , 2975 , 2931 , 1757 , 1715 , 1602 , 1494 , 1453 , 1391 , 1367 , 1315 , 
 1286 , 1270 , 1243 , 1166 , 1070 , 1026 , 986 , 949 , 915 , 889 , 870 , 834 , 
 782 , 759 , 730 , and 650 cm . tlc rf ( 2:1 hexanes / etoac ) = 
 0.50 . the ptx - silicate 
 ( 10 mg ) was dissolved in 900 l of acetone - d6 . to this homogeneous solution , 100 l of a 9:1 
 v / v solution of d2o / tfa was added , and the solution was 
 vigorously mixed . h nmr spectra were taken ( 16 or 32 transients ) 
 at 500 mhz at multiple time points ( 830 ) over the course of 
 more than 3 half - lives for all but the slowest reacting silicates . the study was conducted at room temperature ( 22 c  1.0 
 c ) . typically , resonances for the 2- and/or 
 7-methine protons for the starting taxane silicate and the product 
 free taxane ( ptx or dtx ) vs that of h5 ( a remote proton whose chemical 
 shift was invariant for the two species ) were integrated in a baseline - corrected 
 spectrum using mestre - c or inmr software . data were plotted as growth 
 or decay curves as ln[species  observed ] vs time . the indicated errors are the observed standard deviation 
 from three replications of the experiment . the t1/2 values were calculated under the assumption that the process 
 was pseudo - first - order . the krel data 
 presented in table 2 are the ratios of kobs for each silicate divided by that for the 
 most slowly hydrolyzed silicate ( 1d ) . mda - mb-231 and mda - mb-231 luciferase positive cells were maintained independently in minimum essential 
 medium ( mem ) supplemented with 1% penicillan / streptomycin and 10% 
 fetal bovine serum ( fbs ) at 37 c in a humidified incubator . mda - mb-231 luc+ cells were obtained from caliper life sciences . for 
 cytotoxicity studies , mda - mb-231 cells were seeded at 8000 cells / well 
 in a 96-well plate in 100 l of mem with 5% fbs . taxane and 
 taxane silicate stock solutions ( 10 mm ) were prepared in dmso . each 
 stock solution was serially diluted in mem with 5% fbs , and an amount 
 of 100 l of the solutions was pipetted into the 96-well plate . concentration ranges were from 1 to 10  000 nm for ptx - silicates 
 and from 0.1 to 1000 for dtx - silicates . after 72 h , 30 l of 
 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium ( mtt ) bromide 
 reagent was added to each well . absorbance at 490 nm was monitored 
 on a 96-well plate uv / vis detector at 60 min . viable cells reduce 
 the tetrazolium compound , and the absorbance ( and the concentration ) 
 of the product correlates to the number of viable cells . ic50 values were determined by nonlinear regression analysis of log of 
 concentration vs response data obtained from the mtt assay . the ic50 was interpolated from the resulting curves using graphpad 
 prism , version 5.1 .
we report here the synthesis and 
 selected properties of various 
 silicate ester derivatives ( tetraalkoxysilanes ) of the taxanes paclitaxel 
 ( ptx ) and docetaxel ( dtx ) [ i.e. , ptx - osi(or)3 and dtx - osi(or)3 ] . 
 both the hydrophobicity and hydrolytic lability of these 
 silicates can be ( independently ) controlled by choice of the alkyl 
 group ( r ) . 
 the synthesis , structural characterization , hydrolytic 
 reactivity , and in vitro cytotoxicity 
 against the mda - mb-231 breast cancer cell line of most of these derivatives 
 are described . 
 we envision that the greater hydrophobicity of these 
 silicates ( vis -  - vis ptx or dtx itself ) should be advantageous 
 from the perspective of preparation of stable aqueous dispersions 
 of amphiphilic block - copolymer - based nanoparticle formulations .