Unified Total Syntheses of Benzenoid Cephalotane-Type Norditerpenoids: Cephanolides and Ceforalides

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Oct 5

PMID 36198090

Authors

Goh Sennari

Kristen E Gardner

Stefan Wiesler

Maximilian Haider

Alina Eggert

Richmond Sarpong

Affiliations

Soon will be listed here.

Abstract

Detailed herein are our synthetic studies toward the preparation of the C- and C-benzenoid cephalotane-type norditerpenoids. Guided by chemical network analysis, the core structure of this natural product family was constructed in a concise manner using an iterative cross-coupling, followed by a formal inverse-electron-demand [4 + 2] cycloaddition. Initial efforts to functionalize an alkene group in the [4 + 2] cycloadduct using a Mukaiyama hydration and a subsequent olefination led to the complete C-carbon framework. While effective, this approach proved lengthy and prompted the development of a direct alkene difunctionalization that relies on borocupration to advance the cycloadduct to the natural products. Late-stage peripheral C-H functionalization facilitated access to all of the known cephanolides in 6-10 steps as well as five recently isolated ceforalides in 8-13 steps.

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