羟甲芬太尼立体异构体的晶体结构

CRYSTAL STKUCTURES OF OHMEFENTANYL STEREOISOMERSZX

对强效镇痛剂羟甲芬太尼的两个光学异构体体ｃｉｓ－（３Ｒ，４Ｓ，２′Ｒ）－羟甲芬太尼（Ｉ）和ｔｒａｎｓ－（３Ｒ，４Ｒ，２′Ｓ）－羟甲芬太尼（Ⅱ）进行了Ｘ－射线衍射晶体结构分析。两个异构体均有一个ｓｐ３Ｎ（ｌ）原子和一个ｓｐ２Ｎ（７）原子。哌啶环呈椅式构象，顺式异构体Ｉ的３－甲基处于直立键，４－Ｎ－苯基丙酰胺基处于平伏键；反式异构体ＩＩ的３－甲基与４－Ｎ－苯基丙酰胺基均处于平伏键。在Ｉ分子中，Ｃ（４）原子与４－丙酰胺基组成的平面与Ｎ－苯环平面近似相互垂直，而在ＩＩ中，两平面的二面角近似为１００℃。两异构体分子中均存在分子内氢键Ｏ（１）一Ｈ…Ｎ（１），反式异构体ＩＩ还存在分子间氢键Ｏ（１）一Ｈ（Ａ）…Ｏ（２）（Ｂ）。

Ohmefentanyl,N-[1-(2-hydroxyl-2 phenyl)-3-methyl-piperidyl]-N-phenylpropanamide,is a new and potent analgesic agent.Two stereoisomers :cis-(3R,4S,2′R)-ohmefentanyl(Ⅰ) and trans-( 3R,4R,2′S)-ohmefentanyl(Ⅱ),were selected for X-Ravcrystallographic study.The two isomers were shown tO have an sp3N(1)and an sp2N(7) and thepiperidine ring has a chair conformation,The cis-isomerⅠhas an axial 3-methyl with an equatorial 4-N-phenylpropanamide group, while the two groups of the trans-isomer Ⅱ are all equatorial. In Ⅰmolecule , the plane formed by the 4-propanamide group and atom C(4)is almost perpendicular to the4-N-phenyl ring plane; in Ⅱ, the dihedral angle of the two planes is about 100°. Intramolecularhydrogen bond of O(1)一H…N(1) occurs in both the two isomers and isomer Ⅱ is also involved inintermolecular hydrogen bond O(1)一H(A)…O(2)(B).