Work

A Simple NMR‐Based Rule for Stereochemical Assignment of 1,5‐Diols in Polyketides

Year: 2025

Type: article

Abstract: Polyketide natural products are a valuable source of inspiration for therapeutic lead compounds, but their diversity and complexity make structure elucidation highly challenging. Here, we report a comprehensive analysis of the relative stereochemical assignment of 1,5‐diol moieties in polyketides – a very common but challenging structural element to elucidate. We have found that the chemical shift difference (ΔδHaHb) between the diastereotopic central methylene protons is >0.17 ppm for syn isomers and <0.13 for anti isomers. This simple rule has been shown to correctly predict the relative 1,5‐diol stereochemistries in over 40 natural products, except those cases where the flanking substituents have a large steric difference (tertiary vs primary alkyl) or are constrained within conformationally restricted rings. These resulting ΔδHaHb rules have then been used to predict the relative configuration of several previously unassigned natural products, enabling facile, non‐destructive structure elucidation.

Source: ChemistryEurope

DOI: 10.1002/ceur.202500044

Authors: Max Deering, Malcolm George, Craig P. Butts, Varinder K. Aggarwal

Institution: University of Bristol

Language: English

Topic: Molecular spectroscopy and chirality

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

Open Access status: diamond

Funder: Engineering and Physical Sciences Research Council

Award: EPSRC Centre for Doctoral Training in Technology Enhanced Chemical Synthesis