Approach to the Core Structure of Signermycin B

TL;DR

This paper presents a synthetic approach to the core structure of signermycin B, a natural compound containing a rare cis-decalin ring.

Contribution

The study introduces an anionic oxy-Cope rearrangement to form the cis-decalin core of signermycin B.

Findings

An intramolecular Diels-Alder reaction was used to prepare a tricyclic dienol precursor.

The oxy-Cope rearrangement successfully formed the cis-decalinone structure.

Enolate alkylation introduced a 4-ethyl substituent but resulted in the 4-epi-isomer.

Abstract

Among the natural tetramic acids with a decalinoyl part, signermycin B is unique because it contains a cis‐decalin. In this paper, we demonstrate that the cis‐decalin section of signermycin B can be accessed by an anionic oxy‐Cope rearrangement. The substrate, a tricyclic dienol was prepared by an intramolecular Diels‐Alder reaction of a masked ortho‐benzoquinone, generated by oxidation of an α‐methoxyphenol in presence of cis‐2‐hexenol. After a superfluous bromine on the cycloadduct was removed, reaction of the tricyclic ketone with isopropenylmagnesium bromide led to the tricyclic trienol that underwent the oxy‐Cope rearrangement to a cis‐decalinone. While we could show, that introduction of the 4‐ethyl substituent (signermycin B numbering) is possible by enolate alkylation, the 4‐epi‐isomer was formed.

A tactical sequence of an intramolecular Diels‐Alder reaction of a masked ortho‐benzoquine, tethered to cis‐2‐hexenol, led to a tricyclic ketone which was reacted with isopropenylmagnesium bromide. This led to the substrate for an anionic oxy‐Cope rearrangement, setting the cis‐decalin stereochemistry, required for the core structure of signermycin B.

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