Total Synthesis of Calicheamicin γ₁^I. 3. The Final Stages

The first total synthesis of calicheamicin γ₁^I (1) has been achieved. The stereoselective glycosidation, joining the appropriately functionalized aglycon 3 with the oligosaccharide fragment 2, was realized using Schmidt’s trichloroacetimidate methodology. Segment 4, equipped with the photolabile 2-nitrobenzyl group at the reducing end, was synthesized using similar chemistry to that applied to the synthesis of its methyl glycoside counterpart (see accompanying paper). Stereoselective reduction of oxime 31, obtained from the coupling product, with NaCNBH₃ in the presence of BF₃-OEt₂, late in the synthetic scheme, generated the desired alkoxylamine 32 and its A-4 isomer 32-epi. Installment of the allylic trisulfide and appropriate deprotections allowed transformation of 32 and 32-epi to calicheamicin γ₁^I (1) and its A-4 epimer 1-epi, respectively.