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

ABSTRACT: We report the first total synthesis of samroiyotmycin A (1), a C₂ -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}₄ ].

SUBMITTER: Yiannakas E

PROVIDER: S-EPMC8456858 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Yiannakas Ektoras E Grimes Mark I MI Whitelegge James T JT Fürstner Alois A Hulme Alison N AN

Angewandte Chemie (International ed. in English) 20210720 34

We report the first total synthesis of samroiyotmycin A (1), a C<sub>2</sub> -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 ...[more]

PMID: 34076945

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