New stereoselective approach to hydroxy-substituted tetrahydrofurans. Total synthesis of (±)-citreoviral

Abstract

A concise total synthesis of (±)-citreoviral which illustrates a new stereoselective approach to hydroxy-substituted tetrahydrofurans is described. Key features in the synthesis are: (i) elaboration of the Z-unsaturated epoxy ester 10, (ii) acid-catalysed cyclisation of ester 10 to the 4-hydroxyethyl-substituted but-2-enolide 14, (iii) stereoselective vicinal hydroxylation of the butenolide 14 to the diol15, (iv) cyclic ether formation from diol 15 to the bicyclic lactone 8via the benzylidene acetal 9, (v) transesterification of bicycle 8 to the tetrahydrofuran 21 containing three of the four centres in citreoviral in the correct relative configuration. Inversion of the secondary 3-OH group in compound 21, and elaboration of the C-2 side-chain, then completed the synthesis of (±)-citreoviral.