Access count of this item: 133

Files in This Item:
File Description SizeFormat 
j.tet.2014.11.026.pdf435.97 kBAdobe PDFView/Open
Full metadata record
DC FieldValueLanguage
dc.contributor.authorKikumori, Masayukija
dc.contributor.authorYanagita, Ryo C.ja
dc.contributor.authorIrie, Kazuhiroja
dc.contributor.alternative入江, 一浩ja
dc.date.accessioned2014-12-26T02:25:45Z-
dc.date.available2014-12-26T02:25:45Z-
dc.date.issued2014-12ja
dc.identifier.issn0040-4020ja
dc.identifier.urihttp://hdl.handle.net/2433/192773-
dc.description.abstract10-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.ja
dc.format.mimetypeapplication/pdfja
dc.language.isoengja
dc.publisherElsevier Ltd.ja
dc.rights© 2014 Elsevier Ltd.ja
dc.rightsThis 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。ja
dc.subjectAnticancerja
dc.subjectAplysiatoxinja
dc.subjectPhorbol esterja
dc.subjectProtein kinase Cja
dc.subjectSimplified analogja
dc.titleImproved and large-scale synthesis of 10-methyl-aplog-1, a potential lead for an anticancer drugja
dc.type.niitypeJournal Articleja
dc.identifier.ncidAA00861787ja
dc.identifier.jtitleTetrahedronja
dc.identifier.volume70ja
dc.identifier.issue52ja
dc.identifier.spage9776ja
dc.identifier.epage9782ja
dc.relation.doi10.1016/j.tet.2014.11.026ja
dc.textversionauthorja
Appears in Collections:Journal Articles

Show simple item record

Export to RefWorks


Export Format: 


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.