2. Academic Validation
  3. A practical synthesis of chiral tricyclic cyclopenta[b]benzofuran, a key intermediate of Beraprost

A practical synthesis of chiral tricyclic cyclopenta[b]benzofuran, a key intermediate of Beraprost

  • Org Biomol Chem. 2016 Aug 10;14(32):7715-21. doi: 10.1039/c6ob01346e.
Xiaoyu Liu 1,  Chengsen Tian 2,  Xiaozhen Jiao 1,  Xiaoyu Li 1,  Hongguang Yang 1,  Yangyang Yao 1,  Ping Xie 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China. xp@imm.ac.cn.
  • 2 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China. tiancs@thelilab.cn.
PMID: 27461927 DOI: 10.1039/c6ob01346e
Abstract

A novel formal synthesis of Beraprost (1) is described. The tricyclic cyclopent[b]benzofuran core is efficiently prepared from (-)-Corey lactone diol in 12 steps with an overall yield of 37.4%. Key features of the strategy include a ring-closing metathesis reaction and aromatization to form the tricyclic cyclopenta[b]benzofuran framework, and selective halogenation/formylation to install the butyrate side-chain.

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