Lee J, Marquez V E, Blumberg P M, Krausz K W, Kazanietz M G
Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Bioorg Med Chem. 1993 Aug;1(2):119-23. doi: 10.1016/s0968-0896(00)82109-4.
Starting with L- or D-tri-O-acetylglucal, the corresponding L- and D-isomers of 4-O-tetradecanoyl-2,3-dideoxyglucono-1,5-lactone (2a and 2b) were synthesized as rigid diacylglycerol (DAG) analogues. Consistent with results obtained previously with the equivalent L- and D-1,4-lactones (1a and 1b), the L-isomer (2a) was more potent in activating protein kinase C (PK-C) and inhibiting the binding of [3H]phorbol-12,13-dibutyrate to the enzyme's regulatory domain. In these experiments the difference in potency observed between the optical antipodes of the gluconolactones (2a and 2b) was greatly increased relative to the corresponding ribonolactones (1a and 1b). These results indicate that PK-C is more able to discriminate between optical antipodes, in favor of the L-isomer, as the lactone ring increases from five to six.
从L-或D-三-O-乙酰葡糖醛开始，合成了4-O-十四烷酰基-2,3-二脱氧葡糖酸-1,5-内酯（2a和2b）的相应L-和D-异构体，作为刚性二酰基甘油（DAG）类似物。与先前用等效的L-和D-1,4-内酯（1a和1b）获得的结果一致，L-异构体（2a）在激活蛋白激酶C（PK-C）和抑制[3H]佛波醇-12,13-二丁酸酯与该酶调节域的结合方面更有效。在这些实验中，相对于相应的核糖内酯（1a和1b），葡糖内酯（2a和2b）的旋光对映体之间观察到的效力差异大大增加。这些结果表明，随着内酯环从五元增加到六元，PK-C更能够区分旋光对映体，有利于L-异构体。
