3-(R)-(碱基)-4-(S)-羟基-5-(R)-羟亚甲基四氢呋喃的合成及抗肿瘤活性  

SYNTHESIS AND ANTITUMOR ACTIVITIES OF 3(R)(BASYL)4(S)HYDROXY5(R)HYDROXYMETHYLTETRAHYDROFURANS

作　　者：张虎翼[1] 张铭龙[1] 朴志松 马灵台 张礼和[1] 

机构地区：[1]北京医科大学药学院抗肿瘤药物研究室

出　　处：《药学学报》1999年第5期363-367,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金

摘　　要：目的：研究一系列３（Ｒ）单脱氧异核苷的合成和抗肿瘤活性。方法和结果：由Ｌ木糖出发，合成了环氧化物５（Ｒ）二甲氧甲基３（Ｓ），４（Ｓ）环氧四氢呋喃４；在碱性条件下，利用嘌呤的Ｎ９位或嘧啶的Ｎ１位对环氧化物进行亲核进攻，得到一系列３（Ｒ）单脱氧异核苷５ａｄ和６ａｄ；并进行了体外抗肿瘤活性筛选。结论：其中３（Ｒ）单脱氧异核苷５ａｄ为首次报道；同已报道的３（Ｓ）单脱氧异核苷合成方法相比，路线缩短，收率提高。在体外抗肿瘤和端粒酶抑制活性筛选中，只有化合物６ａ显示了对ＢＩＵ细胞较弱的抑制活性，其余均未显示有意义的抗肿瘤活性和端粒酶抑制活性。AIM: The synthesis and antitumor activities of a series of 3(R)monodeoxynucleosides were studied. METHODS and RESULTS: 5(S)Dimethoxymethyl3(S),4(S)expoxyltetrahydrofuran 4 was obtained in 3 steps from Lxylose. 3(R)(Basyl)4(S)hydroxy5(R)hydroxymethyltetrahydrofuran 5ad and 6ad were synthesized by treating 4 with nucleobase under basic condition, in which comounds 5ad ( a . B=A; b . B=T; cBZ. B=U; d . B=C) were reported firstly. CONCLUSION: The antitumor activity and inhibition of telomerase were determined in vitro. Only compound 6a showed lower inhibition activity for BIU tumor cells.

关 键 词：异核苷 对映体 抗肿瘤活性 

分 类 号：R979.1[医药卫生—药品] R914.5[医药卫生—药学]