Department of Chemistry, University Bayreuth, Universitaetsstr. 30, D-95440 Bayreuth, Germany.
Department of Microbial Drugs, Helmholtz Centre for Infection Research GmbH, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Org Biomol Chem. 2021 Jun 2;19(21):4743-4751. doi: 10.1039/d1ob00717c.
The fungal macrolide berkeleylactone A was synthesised in 13 steps and 24% yield using (R)-propylene oxide and an asymmetric Noyori hydrogenation of a β-ketoester to install the stereogenic centres. A domino addition-Wittig olefination of a 13-hydroxytetradecanal intermediate with the cumulated ylide Ph3PCCO closed the macrocyle by establishing the α,β-unsaturated ester group, necessary for the attachment of the sidechain thiol via a thia-Michael reaction. The synthetic berkeleylactone A inhibited the formation of Staphylococcus aureus biofilms and showed significant dispersive effects on preformed biofilms of Candida albicans by at least 45% relative to untreated controls at concentrations as low as 1.3 μg mL-1.
真菌大环内酯伯克利内酯 A 经 13 步反应、以 24%产率合成，使用 (R)-环氧丙烷和不对称的诺里加氢还原β-酮酯以引入手性中心。十四烷醇醛的 13-羟基与累积叶立德 Ph3PCCO 的加成-威蒂希烯烃化反应通过形成α,β-不饱和酯基完成大环，这是通过硫迈克尔加成反应连接侧链硫醇所必需的。合成的伯克利内酯 A 抑制金黄色葡萄球菌生物膜的形成，并对白色念珠菌的已形成生物膜表现出显著的分散作用，在低至 1.3μg/mL 的浓度下，相对于未处理的对照物至少有 45%的相对分散效果。
