The ''hydrophobic collapse'' conformation of paclitaxel (Taxol(R)) has been observed in a non-aqueous environment: Crystal structure of 10-deacetyl-7-epitaxol

被引:34
作者
Gao, Q [1 ]
Parker, WL [1 ]
机构
[1] BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,NEW BRUNSWICK,NJ 08903
关键词
paclitaxel; paclitaxel side chain; 10-deacetyl-7-epitaxol; conformation;
D O I
10.1016/0040-4020(95)01062-9
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Together with the crystal structure of paclitaxel, this single-crystal X-ray diffraction study of 10-deacetyl-7-epitaxol provides examples of the ''hydrophobic collapse'' conformation of paclitaxel in solid state. More importantly, it gives the first evidence that the ''hydrophobic collapse'' conformation exists ina non-aqueous environment. This study demonstrates that in solid state, a bioactive molecule could adopt a conformation which is usually held only in an aqueous medium through the process of hydrophobic collapse. The special arrangement of molecules and large solvent channels found in the crystal structure suggest a similarity of the molecular environment between the solid state and the aqueous solution. Comparison to the crystal structure of docetaxel (Taxotere(R)) reveals that the flexibility around C1'-C2' and C2'-C3' appears to be fully responsible for the orientation of the side chain. Moreover, a careful comparison of the crystal structures has indicated that the non hydrophobic collapse conformation found in the crystal of paclitaxel is probably caused by molecular packing. It is a common feature for molecules of docetaxel paclitaxel and 10-deacetyl-7-epitaxol that the 2'-hydroxyl and the 4'-carbonyl groups are involved in molecular interactions by hydrogen bonding.
引用
收藏
页码:2291 / 2300
页数:10
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