Molecular Design, Syntheses, and Utilization of New Thiazole-Related Compounds

在对噻唑类化合物的分子设计、合成和利用的研究过程中，我们开发了一些新的杂环化合物，这些化合物涉及分子内无键S【三键】X （X = O， N， S，卤素）相互作用，并合成了一些新的具有药理意义的化合物。在2-（呋喃或噻吩-2-基）1,3噻唑的x射线晶体结构中，均观察到化学特异性非键O【三键】S或S【三键】N相互作用。我们合成了一个萤火虫荧光素和单、双、三噻唑衍生物的模型化合物，通过x射线晶体学分析证实了每个非键S【三键】N相互作用的存在。模型分子的DFT计算表明，具有S【三键】N相互作用的分子在相对能量上是最稳定的。四种2-（2-卤代苯基）- 1,3噻唑衍生物中第一个非键S【三键】X（X = F, Cl, Br， I）相互作用已用上述相同的方法得到证实。有趣的是，三噻唑衍生物在体外对一些人类癌细胞表现出相当大的抗癌活性。在利尿剂乙酰唑胺和基质溶解素抑制剂噻二唑啉硫酮的晶体结构中，即使在它们与碳酸酐酶I、II和基质溶解素的复合物结构中，也观察到类似的非键S【三键】O相互作用。以氮杂环丁烷为原料，高效合成了新型口服碳青霉烯类抗生素的悬垂分子（巯基氮杂二基噻唑啉）。用一种新型红外荧光标记剂（吲哚菁绿酰基噻唑烷硫酮）标记的抗体诊断微癌

In the course of studies on molecular design, syntheses, and utilization of thiazole-related compounds, we have developed several new heterocyclic compounds involving intramolecular nonbonded S【triple bond】X (X = O, N, S, halogens) interactions and new syntheses of pharmaceutically interesting compounds. In each X-ray crystallographic structure of 2-(furan or thiophen-2-yl)1, 3 thiazole, chemospecific nonbonded O 【triple bond】 S or S 【triple bond】 N interaction was observed. We have synthesized a model compound of firefly luciferin and mono-, bi-, and tri-thiazole derivatives, in which the existence of each nonbonded S 【triple bond】 N interaction was confirmed by their X-ray crystallographic analyses. The DFT calculation of their model molecules could support that the molecule bearing such an S【triple bond】N interaction was most stable in relative energy among several ones. The first nonbonded S【triple bond】X(X = F, Cl, Br, I ) interactions in four kinds of 2-(2-halophenyl)-1, 3thiazole derivatives have been demonstrated in a same manner as described above. Interestingly, a tri-thiazole derivative exhibited considerable anticancer activities against some human cancer cells in vitro. The nonbonded S 【triple bond】 O interaction in the crystalline structures of diuretic acetazolamide and stromelysin-inhibitors, thiadiazolinethiones, was similarly observed even in their complex structures with carbonic anhydrase I and II and stromelysin. The pendant molecule (mercaptoazetidinyl thiazoline) of a new oral carbapenem antibiotic was efficiently synthesized by using azabicyclobutane. The antibody labeled with a new infrared fluorescent-labeling agent (indocyanine-green-acylthiazolidinethione ) was utilized for diagnosing microcancers