Retrosynthetic and synthetic chemistry on amphotericin B. Synthesis of C(1)–C(20) and C(21)–C(38) fragments and construction of the 38-membered macrocycle

Abstract

For the first time, amphotericin B (I) has been successfully derivatized and degraded to intermediates that have been converted into compounds (II)[C(1)–C(20) fragment] and (III)[C(21)–C(38) fragment], projected as major key intermediates for a total synthesis; methods have been developed for the coupling of fragments (II) and (III) to give the ketophosphonate–aldehyde (28) and for the cyclization of this preculrsor to the 38-membered macrocyclic heptaenone (29) in 70–80% yield.