A Unifying Bioinspired Synthesis of (-)-Asperaculin A and (-)-Penifulvin D

Overview

Journal Org Lett

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2021 Apr 8

PMID 33830776

Citations 1

Authors

Ian R George

Miguel Lopez-Tena

Anders P Sundin

Daniel Strand

Affiliations

Soon will be listed here.

Abstract

The first syntheses of the isomeric dioxafenestrene natural products (-)-asperaculin A and (-)-penifulvin D are reported. Each target is formed selectively by choice of oxidant in a final divergent bioinspired Baeyer-Villiger (BV) reaction. Density functional theory calculations reveal that electrostatic interactions between the oxidant leaving group and the lactone motif accounts for a reversal of selectivity with HO/HO compared to peracids. Synthetic features include forging the polycyclic carbon framework with a diastereoselective -photocycloaddition biased by an ether substituent at the aryl α-position. The encumbered tertiary alcohol was installed by cyanation of a ketone intermediate followed by nonaqueous hydrolysis of the resulting delicate cyanohydrin.

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