Solid-Phase Synthesis of a Combinatorial Methylated (±)-Epigallocatechin Gallate Library and the Growth-Inhibitory Effects of these Compounds on Melanoma B16 Cells

被引：14

作者：

Tanaka, Hiroshi ^{[1
]}

Yamanouchi, Maasa ^{[1
]}

Miyoshi, Haruko ^{[1
]}

Hirotsu, Keisuke ^{[2
]}

Tachibana, Hirofumi ^{[2
]}

Takahashi, Takashi ^{[1
]}

机构：

[1] Tokyo Inst Technol, Grad Sch Sci & Engn, Dept Appl Chem, Tokyo 1528552, Japan

[2] Kyushu Univ, Fac Agr, Dept Biosci & Biotechnol, Fukuoka 8128581, Japan

来源：

CHEMISTRY-AN ASIAN JOURNAL | 2010年 / 5卷 / 10期

关键词：

combinatorial chemistry; microreactors; phytochemistry; receptors; solid-phase synthesis; KDA LAMININ RECEPTOR; GREEN TEA; ENANTIOSELECTIVE SYNTHESIS; EPIGALLOCATECHIN-3-GALLATE EGCG; PRIVILEGED STRUCTURES; PARALLEL SYNTHESIS; SURFACE BINDING; DERIVATIVES; CATECHIN; INVOLVEMENT;

D O I：

10.1002/asia.201000372

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We report on the solid-phase synthesis of a combinatorial methylated (+/-)-epigallocatechin gallate (EGCG) library and its biological evaluation. Epigallocatechin gallate (EGCG) and its methylated derivatives, which are members of the catechin family, exhibit various anti-cancer effects. The solid-phase synthesis of methylated EGCG involves the preparation of the alpha-acyloxyketone by the coupling of a solid-supported aldehyde with a ketone and an acid. The subsequent release and reductive etherification reaction of the solid-supported alpha-acyloxyketone provide the protected EGCG in good total yields. Sixty-four methylated EGCGs were successfully prepared. The growth-inhibitory effects of the methylated EGCG library were also examined. Although methylation of EGCG generally causes reduced growth inhibition, the growth-inhibitory effect of 7-OMe EGCGs was comparable to that of EGCG. The 7-OMe EGCGs are attractive drug candidates because of their enhanced bioavailability.

引用

页码：2231 / 2248

页数：18

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