設計與合成A環C-8及C環C-2含氧基之比咯苯偶氮駢抗癌烷化試劑

Pyrrolo[2,1-c][1,4]benzodiazepines （PBDs）是由鏈黴菌所產生的一種抗癌抗生素。據推測其抗癌機制是與DNA的窄溝中的鳥糞嘌呤的N2位置上進行共價結合，此作用可抑制癌細胞的DNA複製與增生，以達到抑制癌細胞生長的抗癌作用。並且，在已發表的研究論文中發現，丙烯基與其環氧基亦具有與DNA中的腺嘌呤進行共價鍵結。因此，我們希望合成A環C8位置與C環C2位置含有Epoxide官能基的PBD衍生物。在進行亞胺化後，PBD衍生物便具有三個位置與DNA鍵結。所以，本論文目的在於合成在A環C8位置與C環C2位置同時含有丙烯基與其環氧基的新合成途徑，我們希望合成新的三效PBDs衍生抗癌烷化試劑。

關鍵字

抗癌烷化試劑

並列摘要

Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) were isolated from streptomyces species and belong to an antitumour antibiotics. These compounds are known to exhibit antitumour activity based on their covalent binding ability to the N2 of the guanine residues in the minor groove of DNA. Allylic and its epoxide groups are also known to exhibit antitumour based on their covalent binding ability to adenine residues in the same mechanism as PBDs. We obtain a compound including imine and epoxide functional groups for the better antitumour activity. In this thesis, we describe the synthesis of new analogues of PBDs which contain allylic or its epoxide groups at A ring C8 and C ring C2.This is the first reported trifunctional PBD analogues.