Cytochalasan synthesis: total synthesis of the naturally occurring [13]cytochalasan proxiphomin

Abstract

Proxiphomin (1), a naturally occurring [13]cytochalasan, has been synthesized by a route which uses an intramolecular Diels–Alder reaction of the long chain 3-(1-oxotrienyl)pyrrol-2(5H)-one (18) to form the 13-membered ring. This cyclization gave a mixture of endo and exo isomers (19) and (21), the endo isomer (19) being carried through to proxiphomin. Although the endo–exo selectivity was small, (19) : (21)= 52 : 48, the Diels–Alder cyclization was useful in that no epimerization had occurred at C-5. Cyclization of a mixture of Diels–Alder precursors (18) and (33) prepared from racemic pyrrolidinone (32) gave all four cyclized products (19), (21), (34), and (36) which were 1-debenzoylated, separated, and characterized.