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Synthesis of New Camptothecin Analogues with the E‐Lactone Ring Replaced by α,β‐Cyclohexenone
Author(s) -
Bacherikov Valeriy A.,
Tsai TsongJen,
Chang JangYang,
Chou TingChao,
Lee RongZau,
Su TsannLong
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200600298
Subject(s) - chemistry , camptothecin , lactone , cyclohexenone , stereochemistry , dihydroxylation , intramolecular force , ring (chemistry) , triol , aldol condensation , cytotoxicity , topoisomerase , lactam , diol , organic chemistry , enantioselective synthesis , in vitro , biochemistry , enzyme , catalysis
The total synthesis of racemic camptothecin analogues 12a and 12b , in which the E‐lactone ring has been replaced by an α,β‐cyclohexenone ring and the ethyl and hydroxy substituents have been retained, was achieved by first preparing the ABCD fragments 31a and 31b , which were then converted into the tetracyclic triol 36a and 36b by osmium‐mediated dihydroxylation. Compounds 36a and 36b were oxidized in one‐pot reactions, followed by intramolecular aldol condensation to furnish the desired pentacyclic 12a and 12b , which retained topoisomerase I inhibitory activity and exhibited cytotoxicity to tumor cell growth in culture.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)