Synthesis of Some Nitrosourea Analogues of 5-Aminomethyl-2'- Deoxyuridine

Abstract

本文報告5－胺甲基－2'－去氧尿核?的亞硝基?衍生物的合成，以供抗癌試驗。目前已在臨床試用的亞硝基尿藥物有BCNU，CCNU等，但由於其副作用難於控制，其藥效尚待改進。新近合成的3'－亞硝基尿胸腺核甘具有與BCNU不同的生理活性，另一方面5－胺甲基－2'－去氧尿核甘的水溶性優於3'－亞硝基尿胸腺核甘。因此本研究從可購買得到的胸腺核甘，先製備中間產物5－胺甲基－2'－去氧尿核甘，然後將亞硝基尿類的官能基接於5－胺甲基上，以期改進亞硝基尿類藥物的治癌療效，由胸腺核甘起，經6步反應的總產率為4%。本文也報告由核磁共振圖推知亞硝基化合物的構造。

This paper reports the synthesis of some nitrosourea analogues of 5-amino-methyl-2'-deoxyuridine as potential anticancer agents.Nitrosourea derivatives sudh as BCNU and CCNU have been in clinical trials for many years. However, many studies to modify nitrosourea agents have been undergoing mainly due to their side effects.Newly synthesized 3'-nitrosourea analogues of thymidine have shown greater inhibitory activity against some cancer cells than BCNU. On the other hand, 5-aminomethyl-2'-doxyuridine is more soluble in water than 3-nitrosourea thymidine analogues. These facts, thus, prompted the preparation of the title compounds from commercially available thymidine through 5-aminomethy1-2'-deoxyuridine intermediate and then to the nitrosourea analogues, in hope, to imporve the therapeutic index of nitrosourea agents. The total yield from thymidine through 6 steps of reaction is about 4%. The study on the structure of nitrosourea analogues by NMR is also reported.