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

Dedicated to Prof. Dr. Peter Metz on the occasion of his 70^th birthday

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.

Key words

bioactive γ-butyrolactone - diastereoselective synthesis - defined stereotriad - OH-group inversion - oxidation reduction sequence - iodocyclization - ozonolysis

Publication History

Received: 22 September 2023

Accepted after revision: 20 October 2023

Accepted Manuscript online:
20 October 2023

Article published online:
28 November 2023

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