Synthesis 2019; 51(06): 1408-1418
DOI: 10.1055/s-0037-1612059
paper
© Georg Thieme Verlag Stuttgart · New York

A Concise Approach for Producing Optically Pure Carboxylic Acid Segments for the Synthesis of Bicyclic Depsipeptide Histone Deacetylase Inhibitors

Koichi Narita
a  Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
,
Noel Sayar
a  Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
,
Ken Saijo
b  Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan   Email: katoh@tohoku-mpu.ac.jp
,
Chikashi Ishioka
b  Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan   Email: katoh@tohoku-mpu.ac.jp
,
a  Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
› Author Affiliations
Financial support was provided by the Japan Agency for Medical Research and Development (Grant: Translational Research Network Program) and Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant: Strategic Research Foundation Program at Private Universities S15110010L).
Further Information

Publication History

Received: 12 November 2018

Accepted after revision: 11 December 2018

Publication Date:
05 February 2019 (eFirst)

Dedicated to Professor Tohru Fukuyama, Nagoya University, Japan on his 70th birthday

Abstract

Optically pure carboxylic acid segments, which are common key intermediates for the synthesis of naturally occurring bicyclic depsipeptide histone deacetylase inhibitors, have been produced efficiently. The method features the chromatographic separation of two diastereomers, which were formed by direct amide condensation of racemic (3RS,4E)-3-hydroxy-7-mercaptohept-4-enoic acid (rac-Hmh) with chiral amino acids. This approach offers a reliable and practical method for producing optically pure carboxylic acid segments, which can facilitate easier access to important anticancer agents derived from them.

Supporting Information

 
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