See Table See Table See Table See granatoine (1-4) may be structurally misassigned, as the epimerization of the C5 position is not likely to occur. Therefore, we turned to the total synthesis of this class of limonoids to help resolve this issue. In addition, the bislactone limonoid alkaloids were especially compelling as it is these members that were reported to exhibit modest PTP1B inhibition. Our general retrosynthetic logic toward the bislactone alkaloids entailed the fragment coupling and tandem pyridine synthesis of an AB-and DE-fragment (Scheme 10), akin to our approach to xylogranatopyridine B (1-1). It was speculated that an analogous late-stage benzylic oxidation of C3-deoxyxylogranatin F (10-1) could introduce the requisite C3-oxidation state after unifying the two components together. Several strategies were considered to allow for expedited access to this core architecture (10-1). A Liebeskind pyridine synthesis (cf. Scheme 8-9), 7c between stannane 3-6 and oxime 10-2 could furnish C3-deoxy-xylogranatin F (10-1) directly. An alkylation approach was also considered between allylic bromide 10-3 and α-sulfonyl oxime 10-6, which after sulfone elimination and 6π-electrocyclization, could form 3-deoxy-xylogranin F (10-1). Alternatively, by swapping the R 1 and R 2 substituent on the two fragments, a polarity-reversed alkylation sequence between allylic sulfone 10-4 and α-bromo oxime 10-5 could be envisaged. Complementary approaches involving a Mukaiyama aldol between aldehyde 10-7 and enoxysilane 10-8 followed by condensation, or a Knoevenagel condensation between aldehyde 10-7 and 1,3-diketone 10-9, which would allow for early introduction of the C3-oxidation state, were also imagined to assemble the core structure in 1-2 after condensation of an ammonia equivalent and 6π-electrocyclization.