Zalkow L H, Glinski J A, Gelbaum L T, Moore D, Melder D, Powis G
School of Chemistry, Georgia Institute of Technology, Atlanta 30332.
J Med Chem. 1988 Aug;31(8):1520-6. doi: 10.1021/jm00403a008.
The C-9 and C-7 monoesters and C-7, C-9 diesters of heliotridine with (S)-(+) and (R)-(-)-2-hydroxy-2-phenylbutyric acid were prepared, converted into their N-oxides, and compared with the corresponding C-9 monoesters of retronecine in the in vivo P388 lymphocytic leukemia screen. Relative in vitro cytotoxicities of some of the free bases and their corresponding N-oxides were also measured against the A204 rhabdomyosarcoma cell line by using the soft agar colony forming assay. Stereochemistry at C-7 of the necine and at C-2' of the necine acid appears to have a significant effect on the antitumor activity in this system. In the heliotridine series, the configuration of the necic acid has a pronounced effect on the site selectivity (C-7 vs C-9) in esterification with carbodiimidazole. An explanation for this site selectivity is offered.
制备了天芥菜定与（S）-（+）和（R）-（-）-2-羟基-2-苯基丁酸的C-9和C-7单酯以及C-7、C-9二酯，将其转化为相应的N-氧化物，并在体内P388淋巴细胞白血病筛选中与倒千里光裂碱的相应C-9单酯进行比较。还通过软琼脂集落形成试验测定了一些游离碱及其相应N-氧化物对A204横纹肌肉瘤细胞系的相对体外细胞毒性。在该体系中，裂碱的C-7位和裂碱酸的C-2'位的立体化学似乎对抗肿瘤活性有显著影响。在天芥菜定系列中，裂酸的构型对用碳二亚胺酯化时的位点选择性（C-7对C-9）有显著影响。文中给出了这种位点选择性的解释。
