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

Yiannakas, Ektoras; Grimes, Mark I.; Whitelegge, James T.; Fürstner, Alois; Hulme, Alison N.

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].

STREPTOMYCES; MOLYBDENUM; NATURAL products; CONDENSATION

Angewandte Chemie, 2021, Vol 133, Issue 34, p18652

0044-8249

Academic Journal

10.1002/ange.202105732