A nuclear magnetic resonance study of the diastereoisomer complexes formed between a terguride derivative and naproxen

Abstract

ABSTRACT'H NMR (600 MHz) measurements of chemical shift changes were made in acidified (DCI) CD30D/D20 1:9 v/v equimolar solutions of (S)-and (R,S)-6-methoxy-amethyl-2-naphthaleneacetic acid (naproxen) in the presence of l-(3-aminopropyl)-(5R, 8S, lOR)-terguride (AMP-TER). The most significant bonding interactions concurring to the formation of diastereoisomer complexes are seen as chemical shifts in proximity to the positively charged nitrogen N(6)-CH3 and of H(12), H(13), H(14) protons of the ergoline skeleton, both the adducts having an electrostatic term and different I T-stabilizing interactions. Chemical shift data exclude any contribution of the aminopropyl chain to the chiral recognition mechanism. These findings provide an experimental basis for the enantiodiscriminative process accounting for the observed chromatographic resolutions of arylcarboxylic acids on chiral stationary phases derived from AMP-TER. o 1994 wiley-Liss, Inc.KEY WORDS: diastereoisomer complexes, nuclear magnetic resonance spectroscopy, ergot alkaloid derivatives, haproxen enantiomers Two enantiomeric species can only be recognized and discriminated in the presence of a chiral resolving agent. Therefore, resolution of optical isomers by liquid chromatography necessarily requires a chiral selector, commonly bonded to an achiral matrix, to be involved in reversible interactions with the enantiomers, and competing with them in the formation of labile diastereoisomeric complexes. The stability difference between these complexes affects the degree of chiral discrimination. Therefore, models of chiral recognition accounting for observed enantioseparations are of great value, because they may be used to improve the synthesis of chiral stationary phases (CSPs), select suitable CSPs for the resolution of given racemates, or relate absolute configurations of resolved enantiomers to their elution order. Chiral recognition studies also allow the determination of the role of the achiral support in the enantiodiscriminative process.Nuclear magnetic resonance (NMR) spectroscopy has proved to be a powerful tool in the studies of such diastereoisomeric adducts. Shah et aL3 reported a NMR study of the association complexes of the enantiomers of 2,2,2-trifluoro-l-(g-antryl)-ethanol with butoxycarbonyl-(R)-valine. Prkle and Pochapsky4 confirmed through NMR measurements the chiral recognition model based on the Dalgleish three point con~e p t ,~ for selective retention of (3-DNB-leucine amide on a CSP derived from naphthylalanhe. Recently, we reported the separation of the enantiomers of the structurally analogous compounds, terguride and lisuride,7 and of a series of carboxylic acids' on a CSP derived from 1-(3-aminopropyl)-(5R,8S, lOR)-terguride (AMP-TER). Good enantioselectivity was shown by the above CSP toward underivatized 2-arylpropionic acids used as nonsteroidal antiinflammatory drugs (the selectivity factor for naproxen was a = 1.06)' indicating the high degree of chiral recognition and highly specific attractive interactions between the selecto...

Direct resolution of optically active isomers on chiral packings containing ergoline skeleton. 6. Enantioseparation of profens

“…The formation of complexes was assumed in terms of two interactions: -and electrostatic. 36 However, these interactions do not completely explain the enantioseparation of arylpropionic acids. To explain the mechanism of chiral discrimination, the X-ray crystal structure of the (5R, 8S, 10R)-1-allyl-terguride complex with (S)-naproxen was carried out and compared with the X-ray structure of the free selector 32 and the complex between the analogous selector (5R,8S)-1-allyl-lisuride and (S)-naproxen 33 already determined.…”

CEC enantioseparations on chiral monolithic columns: A study of the stereoselective degradation of (R/S)‐dichlorprop [2‐(2,4‐dichlorophenoxy)propionic acid] in soil

“…The chiral recognition mechanism of the selector towards carboxylic acids has been previously studied in detail [19][20][21][22]. Prerequisite for chiral recognition is the interaction between basic nitrogen (proton acceptor) of the selector and the carboxylic group of analyte that stabilizes the diastereomeric complex (S)-herbicide $ (5R,8S,10R)-terguride.…”

“…Before heating, the polymerization solution was purged by helium through the silanized capillary for 10 min. The capillary was filled with a polymerization solution (% w/w) constituted of: 10.16 (GMA), 8.91 (MMA), 19.85 (EGDMA), 53.54 (formamide), 7.56 (1-propanol) and AIBN (0.1% w/w of the monomer mixture), and heated in a GC oven at 587C for 48 h under He pressure of about 2-3 bar. Unreacted compounds were washed with methanol and the column was functionalized with a 0.5 M (1)-1-(4-aminobutyl)-(5R,8S,10R)-terguride solution in ACN (24 h, room temperature).…”

CEC enantioseparations of carboxylic acids on silica‐based monoliths modified with ergot alkaloid derivative

“…The influence of the buffer pH on the enantiodiscrimination of carboxylic acids by terguride-derivarives was explained on the basis of a model of chiral recognition developed by H 1 NMR [21] and by crystallographic studies of the diastereomeric adducts formed between allyl-terguride and dansyl derivatives of amino acids and arylpropionic acids (Scheme 1) [22][23][24][25]. The short distances between N(6) and the carboxylic oxygen in the two diastereomeric adducts, as observed by X-ray measurements, suggest that the proton of the carboxylic acid tends to transfer to the basic nitrogen forming a sort of intermolecular ion interaction bridged by hydrogen bond.…”