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An Alkyne‐Metathesis‐Based Approach to the Synthesis of the Anti‐Malarial Macrodiolide Samroiyotmycin A
Author(s) -
Yiannakas Ektoras,
Grimes Mark I.,
Whitelegge James T.,
Fürstner Alois,
Hulme Alison N.
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202105732
Subject(s) - metathesis , alkyne , chemistry , ring closing metathesis , combinatorial chemistry , stereochemistry , ligand (biochemistry) , salt metathesis reaction , convergent synthesis , total synthesis , sequence (biology) , acyclic diene metathesis , organic chemistry , catalysis , receptor , biochemistry , polymer , polymerization
We report the first total synthesis of samroiyotmycin A ( 1 ), a C 2 ‐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 ].