A Concise Approach for Producing Optically Pure Carboxylic Acid Segments for the Synthesis of Bicyclic Depsipeptide Histone Deacetylase InhibitorsFinancial 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).
Received: 12 November 2018
Accepted after revision: 11 December 2018
05 February 2019 (eFirst)
Dedicated to Professor Tohru Fukuyama, Nagoya University, Japan on his 70th birthday
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.
Key wordssynthetic intermediate - histone deacetylase inhibitor - natural product - bicyclic depsipeptide - total synthesis
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Spiruchostatins A (3) and B (4), see:
Spiruchostatin C (5), see:
Spiruchostatin D (6), see:
Total synthesis of FK228 (1, romidepsin):
Total synthesis of FR901375 (2):
Total synthesis of spiruchostatin A (3):
Total synthesis of spiruchostatin B (4):
Total synthesis of burkholdacs A (7, thailandepsin C) and/or B (8, thailandepsin A):
Total synthesis of thailandepsin B (10):