Greshock Thomas J, Johns Deidre M, Noguchi Yasuo, Williams Robert M
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
Org Lett. 2008 Feb 21;10(4):613-6. doi: 10.1021/ol702957z. Epub 2008 Jan 19.
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.
描述了强效组蛋白脱乙酰酶（HDAC）抑制剂FK228的可扩展合成方法。通过九个步骤实现了制备关键的β-羟基巯基庚烯酸部分的可靠策略，总产率为13%。通过诺伊里不对称氢转移反应，通过还原炔丙基酮以>99:1的对映体过量建立了羟基立体化学。
