Pettit G R, Rhodes M R, Herald D L, Chaplin D J, Stratford M R, Hamel E, Pettit R K, Chapuis J C, Oliva D
Cancer Research Institute, Arizona State University, Tempe 85287-2494, USA.
Anticancer Drug Des. 1998 Dec;13(8):981-93.
The (E)-stilbene isomer (2a) of the (Z)-combretastatin A-4 prodrug (1b) was efficiently prepared from (E)-combretastatin A-4 by a reaction sequence employing phosphorylation (dibenzyl chlorophosphite), cleavage (trimethyliodosilane) of the benzyl ester and reaction of the resulting phosphoric acid with sodium methoxide. The sodium phosphate product (2c) was also found to be an important side-product, presumably from iodine-catalyzed isomerization, when the analogous synthetic route was used to obtain the combretastatin A-4 prodrug (1b). The phosphoric acid precursor of prodrug 1b derived from (Z)-combretastatin A-4 (1a) was converted into a series of metal cation and ammonium cation salts to evaluate effects on human cancer cell growth, antimicrobial activities and solubility behavior.
通过采用磷酸化（二苄基亚磷酸氯）、苄酯裂解（三甲基碘硅烷）以及所得磷酸与甲醇钠反应的反应序列，由（E）-康普他汀A-4高效制备了（Z）-康普他汀A-4前药（1b）的（E）-二苯乙烯异构体（2a）。当使用类似的合成路线获得康普他汀A-4前药（1b）时，还发现磷酸钠产物（2c）是一种重要的副产物，可能来自碘催化的异构化。源自（Z）-康普他汀A-4（1a）的前药1b的磷酸前体被转化为一系列金属阳离子和铵阳离子盐，以评估其对人癌细胞生长、抗菌活性和溶解性的影响。
