著者

大坪 健児

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.120, no.11, pp.1135-1147, 2000-11-01 (Released:2008-05-30)

参考文献数

41

被引用文献数

1 2

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This review summarizes our recent findings in the syntheses of drug metabolites. The metabolites of Grepafloxacin (1) and OPC-14117 (10) were prepared from the common intermediates (5) and (21), respectively. Moreover, treatment of 10 with a model P450 system led to a benzyl alcohol derivative (11) in one step. OPC-31260 (22) was efficiently N-dealkylated using several metalloporphyrins with oxidants to afford three metabolites (23-25). In addition, I succeeded in obtaining the metabolite (23) in high yield from N-oxide (26) not only as an oxygen donor but also as a substrate, there after, in the model P450 system. Optically active metabolites of OPC-29030 (27) were prepared by enzyme-catalyzed enantioselective transesterification of racemic sulfinyl metabolites. On the other hand, a chiral 1, 1'-bi-2-naphthol derivative (38a) was found to be an efficient asymmetric acylating agent for a secondary alcohol (36) which is a valuable intermediate for preparing optically active metabolites of 22. Furthermore, metabolites (45) and (47) of OPC-21268 (44) were prepared using SmI2-induced cyclization and oxidative decarboxylation with Pb(OAc)4 as key steps, respectively.