3-Deazanaplanocin A (3-DNPA)的新合成方法

doi:10.5246/jcps.2010.06.058

3-Deazanaplanocin A (3-DNPA)的新合成方法

李天舒, 陆世芳, 邢磊, 林桂椿, 关注, 杨振军^*

北京大学医学部天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2010-06-02 修回日期:2010-10-15 出版日期:2010-11-30 发布日期:2010-11-30
通讯作者: 杨振军*

A new strategy for the synthesis of 3-deazaneplanocin A

Tian-Shu Li, Shi-Fang Lu, Lei Xing, Gui-Chun Lin, Zhu Guan, Zhen-Jun Yang^*

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2010-06-02 Revised:2010-10-15 Online:2010-11-30 Published:2010-11-30
Contact: Zhen-Jun Yang*

摘要/Abstract

摘要：

3-去氮-Neplanocin A (3-DNPA, 2)是具有很强抗病毒抗肿瘤活性的碳环核苷。发展其有效的合成路线, 有助于其类似物的合成及进一步的生物活性研究。由2,4-二羟基-3-硝基吡啶起始的3-去氮嘌呤合成, 采用一釜反应直接构建咪唑环, 避免了中间体10被氧化; 同时, 碱基合成中副产物11-1的发现和结构确证, 提示了一条合成1-去氮嘌呤的新方法。采用微波辅助方法提高了6-氯-3-去氮嘌呤12 的肼解及随后的Boc保护制备17 的反应产率; 而后者提高了偶联反应N9异构体的比例。全部合成工作经十步反应得到3-DNPA, 总收率11.2%。

关键词: 3-Deazaneplanocin A, 3-去氮腺嘌呤, Neplanocin A, 1-去氮嘌呤

Abstract:

3-Deazaneplanocin A (3-DNPA, 2), an antiviral and antitumor agent, has been synthesized in an optimized procedure in 10 steps, with an increased overall yield of 11.2%. Started from 2,4-dihyroxyl-3-nitropyridine, reduction of nitro group and ring closure of imidazole were carried out in one pot, without the separation of diaminopyridine (10), to give 3-deazapurine (11). Moreover, the conversion of 6-chloro-3-deazapurine (12) to 6-amino-3-deazapurine (13) and the synthesis of N⁶,N⁶,N9-tris-Boc-3-deazadenine (16) was promoted by microwave-aid method. Compound 16 benefited the formation of N9 isomer of 3-DNPA in Mitsunobu reaction.

Key words: 3-Deazaneplanocin A, 3-Deazaadenine, Neplanocin A, 1-Deazapurine

中图分类号:

R916.4

Supporting: Foundation items: National Natural Science Foundation of China (Grant No. 20472006 and 20832008);
^*Corresponding author. Tel.: 86-10-82802503

李天舒, 陆世芳, 邢磊, 林桂椿, 关注, 杨振军^* . 3-Deazanaplanocin A (3-DNPA)的新合成方法[J]. , DOI: 10.5246/jcps.2010.06.058.

Tian-Shu Li, Shi-Fang Lu, Lei Xing, Gui-Chun Lin, Zhu Guan, Zhen-Jun Yang^* . A new strategy for the synthesis of 3-deazaneplanocin A [J]. , DOI: 10.5246/jcps.2010.06.058.