Ester dienolate [2,3]-Wittig rearrangement in natural product synthesis: Diastereoselective total synthesis of the triester of viridiofungin A, A(2), and A(4)

摘要

An ester dienolate [2,3]-Wittig rearrangement was utilized to access the alkylated citric acid skeleton 6 that is characteristic for the viridiofungins and other members of the alkyl citrate family of secondary natural products. The [2,3]-sigmatropic rearrangement of (Z,Z)-15 provided the rearrangement product (+/-)-syn-16 in moderate yield and with very good diastereoselectivity. A Julia-Kocienski olefination efficiently served to connect the polar head (+/-)-syn-26 with the lipophilic tail (32a-c) of the viridiofungins. Amide formation between the racemic viridiofungin precursors 35a-c and the enantiomerically pure amino acid L-tyrosine methyl ester followed by preparative reversed-phase HPLC provided the isopropyl dimethyl ester of viridiofungin A ((+)-39a), A(2) ((+)-39b), and A(4) ((+)-39c) as well as the nonnatural diastereomers (-)-38a-c.