Total synthesis of natural (+)-ambruticin

Article abstract of DOI:10.1016/S0040-4020(01)88025-X

The structurally unique antifungal antibiotic ambruticin (1) has been prepared for the first time in a convergent synthesis. The strategy for its synthesis involved the independent preparation of the enantiomerically pure fragments 19, 31 and 49. The required C(7) - C(8) β-C-glycoside bond was formed by coupling the glycosyl fluoride 19 with the in situ formed vinyl alane derivative 32. Formation of the C(13) - C(14) trans double bond was accomplished by condensation of the sulfone fragment 49 with the aldehyde intermediate 35 leading to the complete skeletal framework of ambruticin. Saponification of 51 and then cleavage of the benzyl protecting groups gave natural ambruticin.