6-N-烷基-6-氮杂-2-氧代-3-氧杂-4-甲氧基-双环[3.1.0]己烷的合成、立体化学及抗癌活性研究

Synthesis,Stereochemistry and Anti-cancer Activity of 6-N-Alkyl-4-methoxy-3-oxa-6-aza-bicyclo[3.1.0]hexan-2-one

以3-溴-5-甲氧基-2(5H)-呋喃酮和伯胺为原料,在均相中用三乙胺作碱性催化剂,可以得到一对非对映异构体(1Z,4E,5Z)-6-N-烷基-6-氮杂-2-氧代-3-氧杂-4-甲氧基-双环[3.1.0]己烷(4)和(1Z,4Z,5Z)-6-N-烷基-6-氮杂-2-氧代-3-氧杂-4-甲氧基-双环[3.1.0]己烷(5).目标分子4和5经IR,1HNMR,13CNMR,EIMS进行了表征,并做了结肠癌细胞(HCT-8)、肝癌细胞(BEL-7402)、人胃癌细胞(BGC-823)、肺腺癌细胞(A549)和人卵巢癌细胞(A2780)的抗癌活性实验,其中5c和5d对HCT-8,BGC-823,A549和A2780等癌细胞有一定的抑制作用.此研究结果不仅丰富了该领域研究的理论基础,而且对某些新型药物的研制具有一定的指导意义.

Pairs of racemic diastereoisomeric aziridine derivatives （4 and 5） were obtained in good yields by Michael addition followed by internal nucleophilic substitution of 3-bromo-5-methoxy-2（SH）-furanone and primary amines. The resulting aziridines were elucidated by IR, ^1H NMR, ^13C NMR and ELMS, and tested for human cancer cell lines including colon cancer （HCT-8）, liver cancer （BEL-7402）, gastric cancer （BGC-823）, pulmonary gland cancer （A549）, and ovary cancer （A2780）, wherein 5c and 5d display good activities against HCT-8, BGC-823, A549 and A2780. This result not only enriches the theoretical basis in this field, but also has a certain guidable significance for the manufacture of some new drugs.