Synthesis of cytochalasans using intramolecular Diels–Alder reactions: an alternative approach to cytochalasin D

Abstract

The macrocycle 25 which has the required functionality around the macrocyclic ring for incorporation into a synthesis of cytochalasin D 1 has been synthesized using an intramolecular Diels–Alder reaction to form the 11-membered ring. The Diels–Alder precursor 24 was prepared in a convergent fashion from the dienyl phosphonate 17, the aldehyde 16 and the pyrrolidinone 21, with phenylselenenylation and oxidative elimination being used to convert the pyrrolidinone 22 into the unstable pyrrolinone 24. The Diels–Alder reaction of the pyrrolinone 24 under high dilution conditions gave the required endo-adduct 25 in a yield of 53% based on the phenylselenopyrrolidinone 23. N-Debenzoylation gave the NH-lactam 26 but preliminary attempts to effect removal of the SEM-groups led to the formation of the methylenedioxy compound 27.

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