ISSN:0899-0042    

DOI:10.1002/chir.530070102

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractTetrahydroisoquinoline alkaloids, which are known to be present not only in plants but also in animals, including mammals, can be considered as condensation products of 2‐phenylethylamines (e.g., catecholamines) with aldehydes (e.g., acetaldehyde) or 2‐oxo acids (e.g., pyruvic acid). In this study the possibility of separating the optical isomers of several tetrahydroisoquinolines by high‐performance liquid chromatography was investigated. For isosalsoline, tetrahydropapaveroline and laudanosoline a good enantiomeric separation could be achieved by applying β‐cyclodextrin‐bonded silica as stationary phase in connection with various mobile phases. With respect to laudanosoline, the addition of β‐cyclodextrin as chiral selector to the mobile phase using a C18reversed‐phase column as stationary phase revealed an even higher resolution when compared with the chiral columns. All tested tetrahydroisoquinolines which could be well separated into enantiomers bear a hydroxyl group at carbon atom 7 as a common structural feature. Those alkaloids substituted with a methoxy group on position 7 instead of a hydroxyl group (e.g., salsolidine) failed to be resolved into their optical isomers. Therefore, the presence of a hydroxyl group on C7 of the aromatic ring seems to be conducive to steric discrimination. However, the separation results for 1‐carboxysalsolinol were unsatisfactory although this molecule possesses a 7‐hydroxyl group. In this case the existence of a carboxyl group on C1 reduced the chiral recognition and thus the enantiomeric resolution. ©

ISSN:0899-0042    

DOI:10.1002/chir.530070103

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe enantiomeric purities of both substrate, 2‐acetoxy‐3‐bromopropylpara‐toluenesulfonate (I), and product, 2‐hydroxy‐3‐bromopropylp‐toluenesulfonate (II) were examined in one analysis. The enzymatic resolution was conducted by Amano lipase AK and the enantiomeric excess as well as the conversion rate were monitored by HPLC analysis utilizing a Chiralcel OD column. After 7 h of reaction, HPLC results indicated that the enantiomeric purities of both substrate (I) and product (II) were greater than 95% and the conversion rate was around 55%. © 1995

ISSN:0899-0042    

DOI:10.1002/chir.530070104

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractA retention model for the chiral separation of an uncharged solute, felodipine, on CHIRAL‐AGP, using a micellar mobile phase is proposed. The model assumes the presence of two stereoselective sites and each enantiomer was found to interact with different sites. Addition of a chiral aliphatic alcohol, (+)‐(S)‐2‐octanol, preferentially interacted with the binding site for (−)‐(S)‐felodipine. The monomeric form of the micellar agent (Tween® 20) competed with the enantiomers for the adsorption sites, and the formation of a 1:1 complex between the enantiomers and the micelles was assumed. The retention of the solutes was effectively controlled by adding small quantities (<1.63 × 10−3M) of the nonionic detergent Tween 20 to the mobile phase. Baseline separation was achieved by addition of 1.0 mMn‐octylamine to the mobile phase; 8.14 × 10−4MTween 20 in phosphate buffer pH 7.0. The separation factor (α = 1.74) was unaffected by the detergent concentration in the presence of 1.0 mMn‐octylamin

ISSN:0899-0042    

DOI:10.1002/chir.530070105

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractAn optical resolution of the amide derivatives of ibuprofen and the carbamate‐alkylester derivatives of thetrans‐alcohol metabolite of loxoprofen and an analogous compound, CS‐670, was studied by chiral high‐performance liquid chromatography (HPLC). The chiral columns SUMIPAX OA‐4000 and OA‐4100 were used to investigate the enantiomeric separation behavior of these derivatives using both reversed and normal mobile phases. A better separation factor (α) of the amide and the carbamate ester derivatives was obtained in the normal mobile phase than in the reversed mobile phase HPLC. In addition, the recognition mechanisms of both amide and carbamate ester enantiomers were investigated by1H‐nuclear magnetic resonance (NMR). It is suggested that the important driving forces for the enantiomeric separation are the formation of hydrogen bonding and the charge transfer complex between these derivatives and an active site of the chiral stationary phase. © 1995

ISSN:0899-0042    

DOI:10.1002/chir.530070106

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractKinetics of acid‐catalyzed heteronucleophilic substitution and racemization of enantiomeric MeOX in ethanol and enantiomeric EtOX in methanol were studied by quenching reaction products at various times by neutralization. Enantiomeric contents of remaining substrate and reaction product were determined by chiral stationary phase high‐performance liquid chromatography. The experimental procedure allowed the determination of the stereoselectivity (i.e., the enantiomeric ratio of a substitution product formed from an enantiomerically pure substrate) involved in the heteronucleophilic substitution reactions. The stereoselectivity was found to vary between 58:42 and 87:13, depending on the acid concentration, substrate, solvent, and temperature. The enantiomeric purity of remaining substrates was identical to that of the starting substrate, indicating that the enantiomeric substrates did not undergo a ring‐opening reaction. The results provided additional evidence supporting the mechanism proposed earlier in acid‐catalyzed stereoselective heteronucleophilic and homonucleophilic substitutions and the resulting racemization of enantiomeric 3‐alkoxy‐1,4‐benzodiazepines in alcoholic solvents. © 1995 W

ISSN:0899-0042    

DOI:10.1002/chir.530070107

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractA widely utilized pig liver esterase preparation has been found to be derived essentially exclusively from the cytosolic fraction of pig livers. Esterases in cytosol and microsomes prepared from a fresh pig liver hydrolyzed theS‐ andR‐enantiomers of racemic oxazepam 3‐acetate (rac‐OXA) with specific activity ratios of approximately 2.3:1 and 1:62, respectively. Product formations were analyzed by chiral stationary phase high‐performance liquid chromatography. The commercial pig liver esterase preparation showed greater activity towardS‐OXA than did the esterases in the cytosolic fraction prepared from fresh pig liver. The results established that (i) esterases contained in microsomes and cytosol of pig liver have opposite enantioselectivity in the hydrolysis ofrac‐OXA and (ii) the commercial pig liver esterase preparation has a cytosolic origin. © 1995 W

ISSN:0899-0042    

DOI:10.1002/chir.530070108

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe purposes of this work were (1) to develop a high performance liquid chromatographic (HPLC) assay for the enantiomers of thalidomide in blood, (2) to study their inversion and degradation in human blood, and (3) to study the pharmacokinetics of (+)‐(R)‐ and (−)‐(S)‐thalidomide after oral administration of the separate enantiomers or of the racemate to healthy male volunteers. The enantiomers of thalidomide were determined by direct resolution on a tribenzoyl cellulose column. Mean rate constants of chiral inversion of (+)‐(R)‐thalidomide and (−)‐(S)‐thalidomide in blood at 37°C were 0.30 and 0.31 h−1, respectively. Rate constants of degradation were 0.17 and 0.18 h−1. There was rapid interconversion in vivo in humans, the (+)‐(R)‐enantiomer predominating at equilibrium. The pharmacokinetics of (+)‐(R)‐ and (−)‐(S)‐thalidomide could be characterized by means of two one‐compartment models connected by rate constants for chiral inversion. Mean rate constants for in vivo inversion were 0.17 h−1(R to S) and 0.12 h−1(S to R) and for elimination 0.079 h−1(R) and 0.24 h−1(S), i.e., a considerably faster rate of elimination of the (−)‐(S)‐enantiomer. Putative differences in therapeutic or adverse effects between (+)‐(R)‐ and (−)‐(S)‐thalidomide would to a large extent be ab

ISSN:0899-0042    

DOI:10.1002/chir.530070109

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

ISSN:0899-0042    

DOI:10.1002/chir.530070110

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

ISSN:0899-0042    

DOI:10.1002/chir.530070101

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY