Modifications of the MeBmt side chain of cyclosporin A

Dibromocarbene was added to the double bond of 2 with formation of dibromocyclopropyl cyclosporin 3 as a single isomer. Reduction of 3 gave 4. Hydrolysis with fluoride led to the unprotected cyclosporin 5. Removal of the silyl protecting group from 3 gave 6, which could also be obtained directly from 1. The dibromocyclopropyl compound 6 was transformed to the allene 7 (mixture of diastereoisomers). The aldehyde 8 was converted to 9 and rearranged to 10 (single isomer). Oxidation of 1 with Jones reagent gave the ketone 11 (single isomer).