NUCLEOSIDES AND NUCLEOTIDES .97. SYNTHESIS OF NEW BROAD-SPECTRUM ANTINEOPLASTIC NUCLEOSIDES, 2'-DEOXY-2'-METHYLIDENECYTIDINE (DMDC) AND ITS DERIVATIVES

被引：115

作者：

MATSUDA, A ^{[1
]}

TAKENUKI, K ^{[1
]}

TANAKA, M ^{[1
]}

SASAKI, T ^{[1
]}

UEDA, T ^{[1
]}

机构：

[1] KANAZAWA UNIV,CANC RES INST,KANAZAWA,ISHIKAWA 920,JAPAN

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 02期

关键词：

D O I：

10.1021/jm00106a049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new type of antineoplastic nucleoside, 2'-deoxy-2'-methylidenecytidine (DMDC) has been synthesized from the corresponding 2'-keto pyrimidine nucleosides 3 and 8 by the Wittig reaction. During the course of the reaction, we found that an intermediate betaine could pick a proton from the excess triphenylphosphonium bromide to form the 2'-phosphonium salts 5 and 10, which could be further converted into the 2'-deoxy-2'-methylidene nucleosides 4 and 9 by treatment with sodium hydride. Various 5-substituted DMDC derivatives 19a-e,h and their uracil congeners 16a-h were also synthesized from the corresponding 5-substituted uridines 12a-f,h. Among them, DMDC as well as 2'-deoxy-2'-methylidene-5-fluorocytidine (19a) showed potent antileukemic activity against murine L1210 cells in culture. The activity of DMDC and 19a toward various human tumor cells in culture compared with 1-beta-D-arabinofuranosylcytosine and 5-fluorouracil was also examined. In vivo antitumor activity of DMDC against L1210 was also described.

引用

页码：812 / 819

页数：8

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