NEW STEREOSELECTIVE APPROACH TO HYDROXY-SUBSTITUTED TETRAHYDROFURANS - TOTAL SYNTHESIS OF (+/-)-CITREOVIRAL

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 diol 15, (iv) cyclic ether formation from diol 15 to the bicyclic lactone 8 via 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.