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Synthesis 2019; 51(06): 1419-1426
DOI: 10.1055/s-0037-1611707
DOI: 10.1055/s-0037-1611707
paper
Facile Total Synthesis of Thailandepsins D–F: Novel Bicyclic Depsipeptide Histone Deacetylase Inhibitors Isolated from a Microorganism
This study was financially supported by a JSPS KAKENHI (Grant Number: JP15k07865) and a Grant-in-Aid for Strategic Research Foundation Program at Private Universities (Grant Number: S15110010L) from Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).Further Information
Publication History
Received: 12 November 2018
Accepted after revision: 24 November 2018
Publication Date:
01 February 2019 (online)
Dedicated to Professor Kiyoshi Tomioka, Doshisha Women’s College, Japan on his 70th birthday
Abstract
The naturally occurring bicyclic depsipeptide histone deacetylase inhibitors thailandepsins D–F were efficiently synthesized for the first time in 49–61% overall yield over five steps, starting from known amine and carboxylic acid segments. The synthesis includes the condensation of the two known starting materials to directly assemble the corresponding seco-acids, which are the key precursors for macrolactonization. The seco-acids are then macrolactonized using the Shiina method to construct the requisite 15-member macrocycles.
Key words
thailandepsin - histone deacetylase inhibitor - natural products - bicyclic depsipeptide - total synthesis - macrocyclesSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611707.
- Supporting Information
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