Sriharsha Shimoga Nagaraj, Pai Karkala Sreedhara Ranganath, Shashikanth Sheena, Chandra Nagasuma, Prabhu Kandigere Ramaiah
Department of Studies in Chemistry, University of Mysore, Manasagangothri, Mysore, India.
Med Chem. 2007 Sep;3(5):425-32. doi: 10.2174/157340607781745500.
In the search for effective, selective, and nontoxic antiviral and antitumor agents, a variety of strategies have been devised to design nucleoside analogues. Here we have described the versatile synthesis of beta-L-1,3-thiazolidine nucleoside analogues. These analogues are all derived from the key stereochemically defined intermediate N-tert-butoxy-carbonyl-4-hydroxymethyl-1,3-thiazolidine-2-ol which was accessible in 57% yield starting from L-Cysteine methylester hydrochloride. N-tert-butoxycarbonyl-2-acyloxy-4-trityloxymethyl-1,3-thiazolidine was coupled with the pyrimidine bases in the presence of Lewis acids stannic chloride or trimethyl silyl triflate following Vorbruggen procedure. Proof of the structure and configuration was obtained through (1)H NMR, (13)C NMR, Mass, elemental analysis and NOE experiments. Docking and antitumor activity of these nucleoside analogues are also reported.
在寻找有效、选择性且无毒的抗病毒和抗肿瘤药物的过程中，人们设计了多种策略来设计核苷类似物。在此我们描述了β-L-1,3-噻唑烷核苷类似物的通用合成方法。这些类似物均衍生自关键的立体化学定义中间体N-叔丁氧羰基-4-羟甲基-1,3-噻唑烷-2-醇，该中间体可从L-半胱氨酸甲酯盐酸盐开始以57%的产率获得。N-叔丁氧羰基-2-酰氧基-4-三苯甲氧甲基-1,3-噻唑烷在路易斯酸四氯化锡或三氟甲磺酸三甲基硅酯存在下，按照Vorbruggen方法与嘧啶碱偶联。通过(1)H NMR、(13)C NMR、质谱、元素分析和NOE实验确定了结构和构型。还报道了这些核苷类似物的对接和抗肿瘤活性。
