Total Synthesis of Thailandepsin B, a Potent HDAC Inhibitor Isolated from a Microorganism
Total Synthesis of Thailandepsin B, a Potent HDAC Inhibitor Isolated from a Microorganism
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DOI：
10.1248/cpb.c16-00060
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发表时间：
2016-07-01
影响因子：
1.7
通讯作者：
Katoh, Tadashi
中科院分区：
文献类型：
--
作者：
Narita, Koichi;Katoh, Tadashi
从市售的D-正亮氨酸甲酯和已知的（S，E）-3-（4-甲氧基苄氧基）-7-（三苯甲基硫代）庚-4-烯酸出发，经8步反应有效地合成了双环缩酚肽组蛋白脱乙酰酶抑制剂Thailandepsin B，总收率为51%。该方法的特征在于会聚方法，其中相应的开环酸（大环内酯化中的关键前体）通过含D-别异亮氨酸-D-半胱氨酸的片段与含D-正亮氨酸的片段的缩合直接组装。
Thailandepsin B, a bicyclic depsipeptide histone deacetylase inhibitor, was efficiently synthesized in 51% overall yield in eight steps, starting from commercially available D-norleucine methyl ester and known (S,E)-3-(4-methoxybenzyloxy)-7-(tritylthio)hept-4-enoic acid. The method features a convergent approach in which the corresponding seco-acid, a key precursor in macrolactonization, is directly assembled through the condensation of a D-allo-isoleucine-D-cysteine-containing segment with a D-norleucine-containing segment.