Improved total synthesis of the potent HDAC inhibitor FK228 (FR-901228).

Organic Letters
Thomas J GreshockRobert M Williams

Abstract

A scaleable synthesis of the potent histone deacetylase (HDAC) inhibitor FK228 is described. A reliable strategy for preparing the key beta-hydroxy mercapto heptenoic acid partner was accomplished in nine steps and 13% overall yield. A Noyori asymmetric hydrogen-transfer reaction established the hydroxyl stereochemistry in >99:1 er via the reduction of a propargylic ketone.

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Citations

Sep 4, 2013·Journal of Industrial Microbiology & Biotechnology·Lesley-Ann Giddings, David J Newman
Jan 22, 2011·Folia Microbiologica·M DuránN Durán
Jul 23, 2008·Journal of the American Chemical Society·Albert BowersRobert M Williams
Feb 6, 2009·Journal of the American Chemical Society·Albert A BowersJames E Bradner
Mar 28, 2008·Chemical Communications : Chem Comm·Toshiya TakizawaTadashi Katoh
Dec 15, 2010·Journal of Biomedicine & Biotechnology·Shuyang Chen, Nianli Sang
Apr 11, 2018·Topics in Current Chemistry·Ming Wang, Xuefeng Jiang
Jan 13, 2015·Natural Product Reports·Michail TsakosThomas B Poulsen
Oct 5, 2011·Organic & Biomolecular Chemistry·Weiqing HuangXiaoming Zhao
Mar 5, 2019·Current Topics in Medicinal Chemistry·Xiaopeng PengJianjun Chen
Jul 19, 2011·Journal of Peptide Science : an Official Publication of the European Peptide Society·Venugopala K NarayanaswamyThavendran Govender
Oct 18, 2016·Chembiochem : a European Journal of Chemical Biology·Alex R MaolanonChristian A Olsen
Oct 15, 2014·Asian Pacific Journal of Tropical Medicine·Sekar Vinoth KumarAnnamalai Jayakumar
Mar 30, 2011·Organic & Biomolecular Chemistry·Shinichiro FuseTakayuki Doi
Dec 5, 2008·The Journal of Organic Chemistry·Srivari ChandrasekharManika Pal Bhadra
Oct 9, 2008·Journal of Medicinal Chemistry·Salvatore Di MaroJung-Mo Ahn
Jan 23, 2020·Organic Letters·Joyanta MondalRajib Kumar Goswami
Aug 17, 2019·Chemical Reviews·Vijayalekshmi SarojiniGangadhar Sanjayan

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