School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh, EH9 3FJ, UK.
Department of Organometallic Chemistry, Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
Angew Chem Int Ed Engl. 2021 Aug 16;60(34):18504-18508. doi: 10.1002/anie.202105732. Epub 2021 Jul 20.
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} ].
我们报告了 samroiyotmycin A（1）的首次全合成，这是一种从链霉菌属中分离出来的 C 对称 20 元抗疟大环内酯。该收敛性合成策略通过使用前所未有的 Schöllkopf 型缩合反应，在取代的β-内酯上组装双炔片段，并通过雄心勃勃的晚期一锅炔烃交叉复分解-环化复分解（ACM-RCAM）反应进行协调。使用具有三足硅醇配体骨架的最新一代钼卡宾，实现了苛刻的炔烃复分解序列。随后通过使用四聚体簇[{Cp*RuCl}] 催化的现代水合金属化化学转化为所需的 E-烯烃。
