Liu Haining, McCurdy Christopher R, Doerksen Robert J
Department of Medicinal Chemistry, University of Mississippi, MS, 38677-1848, USA.
Theochem. 2010 Apr 15;945(1-3):57-63. doi: 10.1016/j.theochem.2010.01.011.
A conformational search on mitragynine and mitragynaline, natural products isolated from the leaves of Mitragyna speciosa, was performed using the MMFF94s force field and the quantum mechanical B3LYP method. The main difference for the mitragynine conformers is caused by the position of the lone pair of the nitrogen shared by rings 3 and 4. Specifically, the lone pair can be syn or anti to the exocylic ethyl group on ring 4. Syn was found to be lower in energy than anti, because of less steric hindrance between the ethyl and the methylene group adjacent to the N in ring 3. The geometrical parameters for the lowest energy conformer of mitragynine are in excellent agreement with the published X-ray crystal structure's geometry. Because it has one more double bond, mitragynaline has less conformational freedom than mitragynine. The main possible conformational choice in mitragynaline is for orientational flexibility of a C-C single bond in ring 3. The finding of two low energy conformers of mitragynaline differing in ring 3 conformation matches reported X-ray crystal structural data.
使用MMFF94s力场和量子力学B3LYP方法，对从帽柱木（Mitragyna speciosa）叶中分离出的天然产物——帽柱木碱和帽柱木灵进行了构象搜索。帽柱木碱构象异构体的主要差异是由3环和4环共享的氮孤对电子的位置引起的。具体来说，孤对电子可以与4环上的环外乙基处于顺式或反式。由于3环中与氮相邻的乙基和亚甲基之间的空间位阻较小，发现顺式的能量低于反式。帽柱木碱最低能量构象异构体的几何参数与已发表的X射线晶体结构几何结构高度吻合。由于帽柱木灵多一个双键，其构象自由度比帽柱木碱小。帽柱木灵中主要的可能构象选择是3环中碳 - 碳单键的取向灵活性。在帽柱木灵中发现的两个低能量构象异构体在3环构象上不同，这与报道的X射线晶体结构数据相符。
