Facile Total Synthesis of Thailandepsins D–F: Novel Bicyclic Depsipeptide Histone Deacetylase Inhibitors Isolated from a Microorganism

Noel Sayar; Koichi Narita; Tadashi Katoh

doi:10.1055/s-0037-1611707

Synthesis, Inhaltsverzeichnis

Synthesis 2019; 51(06): 1419-1426
DOI: 10.1055/s-0037-1611707

paper

Facile Total Synthesis of Thailandepsins D–F: Novel Bicyclic Depsipeptide Histone Deacetylase Inhibitors Isolated from a Microorganism

Noel Sayar

,

Koichi Narita

,

Tadashi Katoh *

Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan eMail: katoh@tohoku-mpu.ac.jp

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Abstract

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Dedicated to Professor Kiyoshi Tomioka, Doshisha Women’s College, Japan on his 70^th 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 - macrocycles

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Referenzen

References
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