A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

TL;DR

This paper introduces a new method using chiral LC–MS to accurately determine the stereochemistry of a common natural product structure.

Contribution

A novel chiral LC–MS strategy for stereochemical assignment of the MPO moiety in natural products.

Findings

The method combines chemical degradation, synthesis, and chiral LC–MS for high accuracy.

The method was successfully applied to assign the stereochemistry of (+)-capsulactone.

Abstract

A terminal 3-methylpent-4-en-2-ol (MPO) moiety is a common structural feature in various polyketide natural products. Stereochemical assignments of this moiety have mainly relied on computational analyses of NMR, ECD, and specific rotation data. However, none of these approaches can be applied to all compounds. In this study, we developed a method to determine the absolute configuration of the terminal MPO moiety with high accuracy and sensitivity by a combination of chemical degradation, chemical synthesis, and chiral LC–MS analysis. The applicability of this method was demonstrated through the stereochemical assignment of (+)-capsulactone (1).

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