Use of S-t-butyl acetothioacetate in the preparation of milbemycin seco-analogues

Abstract

The preparation of milbemycin seco-analogues are described in which the key step involves alkylation of the γ-carbon atom by acrylaldehyde, or methacrylaldehyde of dianions generated from S-t-butyl acetothioacetate (6). Subsequent protection and transesterification of the products of these reactions with a model spiro acetal unit (1) gave acetoacetate derivatives. These compounds upon reaction with sodium borohydride and deprotection afforded the seco-species.