三尖杉酯碱衍生物的合成及抗肿瘤活性

Studies on the synthesis and antitumor activity of the derivatives of cephalotaxine alkaloid esters

摘要: 目的设计一条适合制备C_3′-N上不同取代的三尖杉酯碱及桥氧三尖杉酯碱的合成路线。方法以光活的中间体I(2′R，3′S)β-苯基缩水甘油酸酯为原料，经过五步反应得到保护侧链酸VI(4′S，5′R)，以2-DPC/DMAP为缩合剂与母核缩合、酸水解，再用不同的酸酐酰化，得到相应的C_3′-N取代的新酯碱。结果合成7个新酯碱化合物，药理筛选结果表明C_3′-N上取代基对抗肿瘤活性有一定影响。结论为进一步结构修饰提供了依据。

Abstract: AimTo design and synthesize some cephalotaxine and drupacine derivatives with different substituentes on C_3′-N of taxol side chain． MethodsProtective side chain acid VI (4′S，5′R) was prepared from optically active (2′R，3′S) methyl β-phenyl glycidate I in five steps. The desired acids were coupled with cephlotaxine and drupacine respectively in the presence of 2-DPC/DMAP, followed by acidic hydrolysis and acylating to give novel alkloid esters with different substitutes on C_3′-N． Results The seven new esters were studied for antitumor activity, the results showed that the antitumor activity was influenced by the substituentes on C_3′-N． ConclusionIt might provide some rational basis for further structral modification．