Pettit G R, Rhodes M R
Cancer Research Institute, Arizona State University, Tempe 85287-2404, USA.
Anticancer Drug Des. 1998 Apr;13(3):183-91.
Combretastatin A-4 (1) as the phosphate ester prodrug (3d) is a potent antineoplastic and antiangiogenesis substance and is in advanced preclinical development. For the purpose of improving the phosphorylation synthetic sequence from combretastatin A-4, new routes were investigated. The phosphorylation step was found to be considerably improved using in situ-generated dibenzyl chlorophosphite. Cleavage of the benzyl esters employing a trimethylchlorosilane/sodium iodide procedure, followed by treatment with sodium methoxide, led to the water-soluble prodrug (3d) in high yield.
康普瑞他汀A-4（1）作为磷酸酯前药（3d）是一种有效的抗肿瘤和抗血管生成物质，正处于临床前的后期开发阶段。为了改进从康普瑞他汀A-4进行磷酸化的合成序列，研究了新的路线。发现使用原位生成的二苄基亚磷酸氯可显著改善磷酸化步骤。采用三甲基氯硅烷/碘化钠方法裂解苄酯，然后用甲醇钠处理，以高收率得到水溶性前药（3d）。
