Rao K V, Bhakuni R S, Johnson J, Oruganti R S
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610, USA.
J Med Chem. 1995 Aug 18;38(17):3411-4. doi: 10.1021/jm00017a026.
10-Deacetylpaclitaxel, isolated from the bark of Taxus brevifolia, was converted into paclitaxel in one composite step (trimethylsilylation, acetylation, and desilylation) and in an overall yield of 80-85%. A series of 10-monoesters of 10-deacetylpaclitaxel are prepared by protection of the 2'- and 7-hydroxyls with a chloroacetyl group, acylation, and deprotection. Depending on the reaction conditions, the 10-monoesters, either exclusively or accompanied by the 2',10-diesters, are formed. The mono- and diesters were evaluated using the L-1210 cell culture assay. The 10-monoesters were comparable to paclitaxel and more active than the corresponding 2',10-diesters. The 10-[(4-methoxyphenyl)acetyl], 10-(2-nitrobenzoyl), and 10-(phenylacetyl) esters were found to be somewhat more active than paclitaxel.
从短叶红豆杉树皮中分离得到的10-去乙酰紫杉醇，通过一个复合步骤（三甲基硅烷化、乙酰化和去硅烷化）转化为紫杉醇，总产率为80-85%。通过用氯乙酰基保护2'-和7-羟基、酰化和脱保护制备了一系列10-去乙酰紫杉醇的10-单酯。根据反应条件，可单独形成10-单酯，或伴有2',10-二酯。使用L-1210细胞培养试验对单酯和二酯进行了评估。10-单酯与紫杉醇相当，且比相应的2',10-二酯更具活性。发现10-[(4-甲氧基苯基)乙酰基]、10-(2-硝基苯甲酰基)和10-(苯乙酰基)酯比紫杉醇的活性略高。
