Synthetic Studies of Amphotericin B. II. A Facile Synthesis of the C-1–C-12 Segments of the Amphotericin B Aglycon

Abstract 3-Deoxy-1,2-O-isopropylidene-α-d-glycero-d-erythro-pentofuranose (11) was stereoselectively converted into the Witting salt 8 corresponding to the C-1–C-6 portion of amphotericin B aglycon (1) in 57% overall yield in 8 steps. The aldehydic segment 9 or 10 corresponding to the C-7–C-12 portion of 1 was also derived in 6 steps from 11 in 53 or 38% overall yield, respectively. Wittig condensation of 8 with 9 or 10 followed by four-step conversion afforded the C-1–C-12 segment, (3S,5R,8R,9R,11S)-1-O-t-butyldimethylsilyl-12-iodo-3,5:8,9-di-O-isopropylidene-11-O-[(2-methoxyethoxy)methyl]-1,3,5,8,9,11-dodecanehexol(4)or(2S,4R,5R,8R,10S)-1,2-anhydro-12-O-t-butyldimethylsilyl-4,5:8,10-di-O-isopropylidene-1,2,4,5,8,10,12-dodecaneheptol (5) in 26 or 15% overall yield from 11, respectively.