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)-HYDROXY-5-(R)-HYDROXYMETHYL-TETRAHYDROFURANS

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。

Abstract: AIM: The synthesis and antitumor activities of a series of 3-(R)-monodeoxynucleosides were studied. METHODS and RESULTS: 5-(S)-Dimethoxymethyl-3(S),4(S)-expoxyl-tetrahydrofuran 4 was obtained in 3 steps from L-xylose. 3-(R)-(Basyl)-4(S)-hydroxy-5-(R)-hydroxymethyl-tetrahydrofuran 5a-d and 6a-d were synthesized by treating 4 with nucleobase under basic condition, in which comounds 5a-d (a. B=A; b. B=T; c. 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.