Mechanistic study of the enantiomeric recognition of a basic compound with negatively charged single-isomer gamma-cyclodextrin derivatives using capillary electrophoresis, nuclear magnetic resonance spectroscopy, and infrared spectroscopy.
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.
Zhou
Lili
L
Merck Research Laboratories, Merck and Co. Inc., PO Box 2000, RY818 C-213, Rahway, NJ 07065, USA. lili_zhou@merck.com
Thompson
Richard
R
Reamer
Robert A
RA
Lin
Zhihao
Z
French
Mike
M
Ellison
Dean
D
Wyvratt
Jean
J
D000081:Acetamides / Q000737:chemistry / Q000302:isolation & purification*; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D000081:Acetamides; D003505:Cyclodextrins; C030686:acetamide