Berkeleylactone A 的全合成。

Total Synthesis of Berkeleylactone A.

机构信息

Faculty of Chemical and Food Technology , Slovak University of Technology , Radlinskeho 9 , 81237 Bratislava , Slovakia.

Department of Chemistry , University of Oxford, Chemistry Research Laboratory , Oxford OX1 3TA , U.K.

出版信息

J Org Chem. 2019 Jun 7;84(11):7159-7165. doi: 10.1021/acs.joc.9b00850. Epub 2019 May 23.

DOI:10.1021/acs.joc.9b00850

PMID:31081630

Abstract

The first total synthesis of the potent antibiotic berkeleylactone A is described in 10 steps with an overall yield of 9.5%. A key step of our concise route is a late-stage, highly diastereoselective, sulfa-Michael addition. The 16-membered macrocyclic lactone was formed via ring closing metathesis and subsequent chemoselective reduction. The absolute stereochemical configuration was confirmed by single-crystal X-ray analysis. Synthetic berkeleylactone A was tested against several methicillin-resistant Staphylococcus aureus strains, and its potent antibacterial activity was verified.

摘要

本文描述了强效抗生素伯克利内酯 A 的首次全合成，共 10 步，总收率为 9.5%。我们简洁路线的关键步骤是晚期、高度非对映选择性的砜迈克尔加成。通过闭环复分解和随后的化学选择性还原形成 16 元大环内酯。通过单晶 X 射线分析确定了绝对立体化学构型。合成的伯克利内酯 A 对几种耐甲氧西林金黄色葡萄球菌菌株进行了测试，验证了其强大的抗菌活性。