Manfredini S, Baraldi P G, Bazzanini R, Marangoni M, Simoni D, Balzarini J, De Clercq E
Departimento di Scienze Farmaceutiche, Università di Ferrara, Italy.
J Med Chem. 1995 Jan 6;38(1):199-203. doi: 10.1021/jm00001a025.
It is well-known that the introduction of vinyl and ethynyl moieties into nucleosides is of crucial importance for cytostatic, antiviral, or other biological activities. In this study 6- and 8-vinyl-and -ethynyluridine and -adenosine were prepared by a general procedure involving the palladium-catalyzed cross-coupling of trimethylsilylacetylene or vinyltributyltin. The introduction of a vinyl group at C-6 of uridine or an ethynyl group at C-8 of adenosine resulted in nucleoside derivatives showing cytostatic activity against several murine and/or human tumor cell lines. Interestingly, 8-vinyladenosine had pronounced selective inhibitory effects on human (Molt/4F and MT-4) versus murine (L1210 and FM3A) tumor cell lines.
众所周知，将乙烯基和乙炔基引入核苷对于其细胞抑制、抗病毒或其他生物活性至关重要。在本研究中，通过涉及钯催化的三甲基硅乙炔或乙烯基三丁基锡交叉偶联的通用方法制备了6-和8-乙烯基-和-乙炔基尿苷及腺苷。在尿苷的C-6位引入乙烯基或在腺苷的C-8位引入乙炔基，得到了对几种小鼠和/或人类肿瘤细胞系具有细胞抑制活性的核苷衍生物。有趣的是，8-乙烯基腺苷对人类（Molt/4F和MT-4）肿瘤细胞系与小鼠（L1210和FM3A）肿瘤细胞系具有明显的选择性抑制作用。
