紫杉醇类似物的合成研究Ⅷ去甲二萜生物碱转化合成紫杉醇类似物的.pdf

四川大学
博士学位论文
紫杉醇类似物的合成研究Ⅷ去甲二萜生物碱转化合成紫杉醇类
似物的研究
姓名:谢光波
申请学位级别:博士
专业:药物化学
指导教师:王锋鹏
20050423
中文摘要
本论文在前期研究工作的棊础上,进一步对ABC合成路线进行了
研究,同时提出了新的转化合成战略,并对其中的关键反应(B环扩环
重排)进行了初步的研究,另外,还研究了NBS/HOAc脱苄基的反应。
以伯胺化合物19为底物,试图进行B环C(7)-C(17)键的Grob裂解,
结果仅得到具有ム85双键的化合物23。这说明在此情况下,A环修饰
后不易裂解C(7)-C(17)键。
以C(のC(の键未裂解而同时具有8.15-双羟基的化合物34,39为
底物,成功的制得了B环重排得中?体40,42,对它们分别进行了重排
反应研究。结果化合物40并未发生 Semipinacol重排,仅仅得到环氧化
物3,而化合物42也未发生 Acyloin重排而只是得到了化合物4,这
说明在B环未修饰的情况下,扩环重排难以实现
以B环经修饰的化合物61,63为底物,出于C(7の取代基的位阻而
并未制得重排的中间体。改变方法,顺利制得具有ムN3双键且C(7)无取
代基的化合物103,该化合物也出于C(14)-OMs位阻而未能制得重排的
中间体。对B环经修饰的化合物85采用新的重排方法(TIN)重排进
行研究,结果仅得到.β-不饱和87。
以化合物131为底物,对NBS/HOAC脱苄基的反应进行了研究,
顺利制得脱苄基的化合物133。
本文共制得90个去甲二帖生物破,其中87个为新的人工产物。新
化合物中多数结构复杂,且颇具新颖性。对所制各的新化合物应用光谱
(MS,1D…-NMR,2D-NMR)和化学方法确定了结构。
Abstract
On the basis of our previous work on the conversion of the
norditerpenoid alkaloids into taxoids, this dissertation described further
research on the ABC route. At the same time. we brought forward a new
conversion stratagem, and study the key reaction primarily. In addition, we
also study the debenzylation with NBS/HOAC
in the research of ABC route, chloronation of 19 possessing C(17)-NH
with SOCL2 in PHH did not give the desired 7.17-seco compound but
compound 23 having 455. This indicated that it is difficult to cleave
7, 17-bond of ring B after the modification of ring A
In the study of the key reaction of ring B rearrangement. we
successfully prepared the key compounds 40, 42 for enlarging of ring B from
the compunds 34 and 39, whose ring B have not been modified. However
attempts are failed together with compounds 35 having 8, 15-epoxy and 44
Such results indicated that the rearrangement is difficult when ring B was not
modified
Due to the spatial resistance of substitute group in C(7). the ke
compound for rearrangement was not prepared by compounds 61 and 63
whose ring B were modified. After changing the strategy, compound 103
without substitute group in C(7)but having A) at the same time was
obtained. But the attempts to synthesis the key compound for
rearrangement was also failed. Compound 85 was used for rearrangement by