Synthesis of (–)-Virginiae Butanolide A (VB-A)

Abstract

The 2-(1’-hydroxyalkyl) paraconyl alcohols (-)-VB-A and (-)-SCB-5 are known as highly active signaling molecules within antibiotics production in Streptomyces sp. These γ-butyrolactone type compounds are epimeric at the 1’-OH-group. A direct synthesis of (-)-VB-A from (-)-SCB-5 that uses a late-stage inversion of the 1’-hydroxy group is not favored because of side reactions of the carbinol in β-position to the lactone C=O function. Therefore, an orthogonally protected 1,4-diol incorporating the central syn/anti 1’,2,3-stereotriad as described within the (-)-SCB-5 synthesis was used as an advanced intermediate to generate (-)-VB-A, too. A combination of protecting group operations and a 1’-OH group inversion via oxidation and diastereoselective reduction delivered the anti/anti 1’,2,3-stereotriad. Final transformations related to that as described for (-)-SCB-5 enabled completion of the (-)-VB-A-synthesis.