An Alkyne-Metathesis-Based Approach to the Synthesis of the Anti-Malarial Macrodiolide Samroiyotmycin A

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2021 Jun 2

PMID 34076945

Citations 12

Authors

Ektoras Yiannakas

Mark I Grimes

James T Whitelegge

Alois Furstner

Alison N Hulme

Affiliations

Soon will be listed here.

Abstract

We report the first total synthesis of samroiyotmycin A (1), a C -symmetric 20-membered anti-malarial macrodiolide isolated from Streptomyces sp. The convergent synthetic strategy orchestrates bisalkyne fragment-assembly using an unprecedented Schöllkopf-type condensation on a substituted β-lactone and an ambitious late-stage one-pot alkyne cross metathesis-ring-closing metathesis (ACM-RCAM) reaction. The demanding alkyne metathesis sequence is achieved using the latest generation of molybdenum alkylidynes endowed with a tripodal silanolate ligand framework. Subsequent conversion to the required E-alkenes uses contemporary hydrometallation chemistry catalysed by tetrameric cluster [{Cp*RuCl} ].

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