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Title: Improved and large-scale synthesis of 10-methyl-aplog-1, a potential lead for an anticancer drug
Authors: Kikumori, Masayuki
Yanagita, Ryo C.
Irie, Kazuhiro  kyouindb  KAKEN_id
Author's alias: 入江, 一浩
Keywords: Anticancer
Aplysiatoxin
Phorbol ester
Protein kinase C
Simplified analog
Issue Date: Dec-2014
Publisher: Elsevier Ltd.
Journal title: Tetrahedron
Volume: 70
Issue: 52
Start page: 9776
End page: 9782
Abstract: 10-Methyl-aplog-1 (1), a simplified analog of tumor-promoting aplysiatoxin, is a potential lead for cancer therapy that exhibits marked and selective growth inhibitory effects against several human cancer cell lines and negligible tumor-promoting activity in vivo. However, more detailed evaluations of its toxicity and anticancer activity in vivo are hampered by supply problems associated with a non-optimal synthetic method. We here addressed this issue through a more practical and reliable synthetic method that afforded several hundred milligrams of 1 with high purity (>98%) in 23 steps from commercially available m-hydroxycinnamic acid with an overall yield of 1.1%. The utilization of two key reactions, substrate-controlled epoxidation and the oxidative cleavage of alkene with a free hydroxyl group, successfully reduced the existing five synthetic steps and markedly improved the handling of large amounts of intermediates. We also demonstrated for the first time that such an analog was synthetically accessible in reliable quantities and also that this large supply could advance in vivo trials for the treatment of cancer.
Rights: © 2014 Elsevier Ltd.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/192773
DOI(Published Version): 10.1016/j.tet.2014.11.026
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