Zhou Lili, Thompson Richard, Reamer Robert A, Lin Zhihao, French Mike, Ellison Dean, Wyvratt Jean
Merck Research Laboratories, Merck and Co. Inc., PO Box 2000, RY818 C-213, Rahway, NJ 07065, USA.
Electrophoresis. 2003 Aug;24(15):2448-55. doi: 10.1002/elps.200305510.
The possible mechanisms for the chiral recognition of 2-(R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide (RR-M3), and its enantiomer (SS-M3) with octakis(2,3-di-O-acetyl-6-sulfo)-gamma-cyclodextrin (ODAS-gamma-CD) and octakis(6-sulfo)-gamma-cycöpdextrom enantiomer; (OS-gamma-CD), were investigated using capillary electrophoresis (CE), proton ((1)H), fluorine ((19)F) and carbon ((13)C) nuclear magnetic resonance spectroscopy (NMR), and infrared (IR) spectroscopy. Clear evidence for the formation of diastereomeric complexes between the enantiomers and the two CDs was observed. NMR spectra suggest that the phenyl and difluorocyclopentyl rings are involved in the complexation. The phenyl ring on the guest molecule is deeply penetrated into the cavity of OS-gamma-CD, but it is not included into the cavity of ODAS-gamma-CD. The continuous variation plots built based on the (1)H NMR and IR spectra indicate a 1:1 complex stoichiometric ratio of the M3 enantiomers for both CDs. The affinity of the enantiomers for the two CDs is opposite.
采用毛细管电泳（CE）、质子（¹H）、氟（¹⁹F）和碳（¹³C）核磁共振光谱（NMR）以及红外（IR）光谱，研究了2-(R)-N-[1-(6-氨基吡啶-2-基甲基)哌啶-4-基]-2-[(1R)-3,3-二氟环戊基]-2-羟基-2-苯基乙酰胺（RR-M3）及其对映体（SS-M3）与八(2,3-二-O-乙酰基-6-磺基)-γ-环糊精（ODAS-γ-CD）和八(6-磺基)-γ-环糊精对映体（OS-γ-CD）之间的手性识别可能机制。观察到对映体与两种环糊精之间形成非对映体复合物的明确证据。核磁共振光谱表明，苯基和二氟环戊基环参与了络合作用。客体分子上的苯环深深地插入到OS-γ-CD的空腔中，但未包含在ODAS-γ-CD的空腔中。基于¹H NMR和IR光谱构建的连续变化图表明，两种环糊精的M3对映体的络合化学计量比均为1:1。对映体对两种环糊精的亲和力相反。
