1 H NMR and LC-MS analysis of the purified benzyl calicheamicin trisulfide clearly indicated the formation of the trisulfide metathesis product without any reaction at the potentially sensitive enediyne. The formation of the MeS3Bn co-product was further confirmed by GC-MS and 1 H NMR spectroscopy after its extraction. Similar results and selectivity were observed in the trisulfide metathesis of calicheamicin with di-n-propyltrisulfide (S209-S210). These results illustrate the exquisite selectivity and functional group compatibility of the novel S-S metathesis reaction. In contrast, a control experiment in which calicheamicin was treated with propane thiol resulted in a complex mixture of products (S211-S213). As a final example of calicheamicin modification, selfmetathesis in DMF was demonstrated with the formation of a calicheamicin dimer and dimethyl trisulfide. Because of the steric bulk of calicheamicin, this reaction was slower than the previous examples but could be accelerated by running the reaction at 40 ºC. 1 H NMR spectroscopy clearly showed the formation of MeS3Me, and LC-MS showed clean equilibration of calicheamicin with its dimer (S214-S216). The cross-metathesis and self-metathesis of the calicheamicin trisulfide highlights the remarkable selectivity of the metathesis reaction, which proceeds under mild conditions and does not compromise the other potentially reactive functional groups such as the enediyne, thioester, or the a,b-unsaturated ketone. The reaction is also selective for trisulfide formation;