Han Fu She, Osajima Hiroyuki, Cheung Mui, Tokuyama Hidetoshi, Fukuyama Tohru
PRESTO, The Japan Science and Technology Agency, Hongo, Tokyo 113-0033, Japan.
Chemistry. 2007;13(11):3026-38. doi: 10.1002/chem.200601446.
The facile synthesis of linear and cyclic chiral oligo(4-alpha/beta-methyl)thiazolines is described. Linear oligothiazolines have been efficiently synthesized by the iterative formation of thiazoline rings and two-directional block condensation. The construction of 24- to 36-membered cyclic oligothiazolines was achieved through the head-to-tail cyclo-oligomerization of doubly deprotected linear fragments. Studies of the interactions of both the linear and cyclic oligomers with chiral compounds revealed that cyclic oligomers displayed a strong binding affinity towards mandelic acid, whereas linear oligomers showed a poor affinity. Linear oligomers have been proven to inhibit the cell growth of the cancer cell lines HPAC, PC-3, and HCT-116. Studies of the structure-activity relationships showed that the IC50 values are clearly dependent on both the length and the terminal functionalities of the linear oligomers. Longer derivatives showed more potent activity (e.g., hexi- and octithiazolines exhibit IC50<1 microM) against all three cancer cell lines. In sharp contrast, cyclic oligomers were inactive to all three cell lines.
本文描述了线性和环状手性低聚（4-α/β-甲基）噻唑啉的简便合成方法。线性低聚噻唑啉通过噻唑啉环的迭代形成和双向嵌段缩合高效合成。通过双脱保护线性片段的头对头环化低聚反应实现了24至36元环状低聚噻唑啉的构建。线性和环状低聚物与手性化合物相互作用的研究表明，环状低聚物对扁桃酸表现出很强的结合亲和力，而线性低聚物的亲和力较差。已证明线性低聚物可抑制癌细胞系HPAC、PC-3和HCT-116的细胞生长。构效关系研究表明，IC50值明显取决于线性低聚物的长度和末端官能团。较长的衍生物对所有三种癌细胞系表现出更强的活性（例如，六聚和八聚噻唑啉的IC50<1 microM）。与之形成鲜明对比的是，环状低聚物对所有三种细胞系均无活性。
