摘要:

AbstractSome 3‐t‐butyldimethylsilyloxy derivatives, synthesized from the cheap commercially available (1S,2S)‐2‐amino‐1‐phenyl‐1,3‐propanediol [(1S,2S)‐1], have been successfully employed as new chiral ligands in the asymmetric Reformatsky reaction on aldehydic substrates. The influence both of the substrate and of the ligand on the stereochemical pathway has been investigated by varying the structure of the carbonyl substrate and of the optically active aminodiols. © 19

ISSN:0899-0042    

DOI:10.1002/chir.530070702

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractHere we present a kinetic study on the steroselectivity and regioselectivity of 23 purified lipases of animal and microbial origin. This work, concerning a general problem of the mechanism of lipase–substrate molecular recognition, was performed using pure dicaprin isomers: 1,2‐sn‐dicaprin, 2,3‐sn‐dicaprin, and 1,3‐sn‐dicaprin spread as monomolecular films at the air–water interface. The first two isomers are optically active antipodes (enantiomers), forming stable films up to 40 mN m−1, while the last is a prochiral compound, with a surface pressure of collapse of 32 mN m−1. To our knowledge, this is the first report on the use of three diglyceride isomers as lipase substrates under identical and controlled physicochemical conditions. The lipases tested display a typical behaviour, characteristic of each enzyme, which allowed us to classify the lipases in groups according to (1) the profiles of enzyme velocity as a function of surface pressure, (2) their preferences for a given diglyceride isomer, quantified using new parameters termed steroselectivity index (S.I.), vicinity index (V.I.), and surface pressure threshold (S.P.T.). The general observation, true for all the enzymes tested, is that the three substrates are well differentiated, and the differentiation is more pronounced at high interfacial energy (low surface pressure). This observation supports our hypothesis that lipase conformational changes, resulting from the enzymesurface interaction, affect the enzymes' specificities. Generally speaking, the stereopreference for eithersn‐1 orsn‐3 position on glycerides is maintained both in the case of di‐ and tri‐glyceri

ISSN:0899-0042    

DOI:10.1002/chir.530070703

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

ISSN:0899-0042    

DOI:10.1002/chir.530070704

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe absolute configurations of the enantiomers of the opiod picenadol [cis‐1,3‐dimethyl‐4‐propyl‐4‐propyl‐4‐(3‐hydroxyphenyl)piperidine;cis‐3‐methyl, 4‐propyl] have been determined by an X‐ray crystallographic study of the chloride salt of the (+)‐enantiomer. The agonist (+)‐enantiomer and the antagonist (−)‐enantiomer were found to have the 3R, 4R and 3S, 4S absolute configurations, respectively. The conformational properties of the enantiomers were also examined with MM2–87 calculations. There was good agreement between the computed global minimum and the crystallographic structure with the phenyl ring approximately bisecting the piperidine ring by both methods. This orientation of the phenyl ring differs from that of related opioids such as the phenylmorphans, prodines, meperidine, and ketobemidone in which the phenyl ring tends to eclipse one edge of the piperidine ring. Because the phenyl ring bisects the piperidine ring in picenadol, there is little difference in the three‐dimensional orientations of the phenyl rings of the two enantiomers when one superimposes the piperidine rings. The agonist (+)‐enantiomer is ambiguous with respect to an opioid ligand model, which suggests that agonist activity requires a specific range of dihedral angles for the phenyl ring. While the global minimum of the agonist is not consistent with the model, a second conformer that is only 1.2 kcal/mol above the global minimum is consistent. An alternative explanation is that agonist or antagonist activity is solely due to the presence of the 3‐methyl group on the different edges of the piperidine ring. MM2–87 calculations were also performed on the opioid agonist des‐3‐methyl analog of picenadol and the closely relatedtrans‐1,3,4‐trimethyl‐4‐(3‐hydroxyphenyl)piperidines (trans‐3‐methyl, 4‐methyl) in which both enantiomers are opioid antagonists. The conformational properties of these compoun

ISSN:0899-0042    

DOI:10.1002/chir.530070705

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have previously shown that (R)‐5‐amino‐4‐hydroxyvaleric acid [(R)‐4‐OH‐DAVA] and (S)‐2‐OH‐DAVA bind to GABABreceptor sites and antagonize GABABreceptor‐mediated function in a stereoselective manner. Furthermore, we have identified energy‐minimized superimposable conformations of (R)‐4‐OH‐ and (S)‐2‐OH‐DAVA which are assumed to reflect the receptor‐active conformations of these compounds. This paper describes the in vitro enantiopharmacology of 5‐amino‐4‐hydroxy‐2‐methylvaleric acid (2‐Me‐4‐OH‐DAVA). Whereas none of the four stereoisomers showed significant affinity for GABAAreceptor sites or GABA uptake mechanisms in rat brain synaptic membranes, (2R,4R)‐2‐Me‐4‐OH‐DAVA was shown to inhibit stereoselectively the binding of [3H]GABA to rat brain GABABreceptor sites (IC50= 14 ± 4 μM). (2R,4R)‐2‐Me‐4‐OH‐DAVA (Ki= 36 μM) and, with much lower potency, (2S,4R)‐2‐Me‐4‐OH‐DAVA (Ki= 370 μM) stereoselectively antagonized GABABreceptor‐mediated function in the isolated guinea pig ileum. The structure of the eutomer, (2R,4R)‐2‐Me‐4‐OH‐DAVA, was established by an X‐ray crystallographic analysis, and the solid‐state conformation of (2R,4R)‐2‐Me‐4‐OH‐DAVA was

ISSN:0899-0042    

DOI:10.1002/chir.530070706

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractIn vitro coenzyme A thioester formation from (−)‐(R)‐fenoprofen (FPF) and palmitic acid has been studied using liver microsomes from rat, guinea pig, sheep, and dog. In every species with both palmitic acid or (−)‐(R)‐fenoprofen, the Lineweaver–Burk plot was linear in the substrate concentration range used and as a consequence agrees with the involvement of only one isoenzyme (or different isoenzymes of similar Kmvalues). The Vmaxvalues for the thioesterification of (−)‐(R)‐fenoprofen present large species variations from 2.1 ± 1.0 with sheep liver microsomes to 60.6 ± 11 nmol/min/mg with dog liver microsomes. These values statistically significantly correlate (r= 0.94) to the Vmaxvalues observed when palmitic acid was used as a substrate. Furthermore palmitic acid inhibited (−)‐(R)‐fenoprofen–CoA formation in the same extent in all animal species. The stereoselectivity of the thioesterification was also species depe

ISSN:0899-0042    

DOI:10.1002/chir.530070707

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractThree endocyclic sulfoximides of the 1‐aryl‐ and 1‐alkyl‐3‐oxo‐benzo[d]‐isothia (IV)‐azole 1‐oxide type (1‐substituent = 2′‐carboxyphenyl, 2′‐carbethoxyphenyl, and octyl, respectively) were found to be well resolved on a chiral phase derived from bovine serum albumin (BSA). Selectivities (α) of 1.74, 1.12, and 1.44, respectively, were obtained. The retention behaviour of 1‐octyl‐3‐oxo‐benzo[d]isothia(IV)‐azole 1‐oxide was further investigated in some detail as a function of the mobile phase composition and the elution order was established from optically active material obtained from the enantiopure sulfoxide precursor. An enantiomeric excess of 85.4% was obtained in the cyclocondensation reaction of the octyl‐substituted sulfoxide precursor with hydrazoic acid to the corresponding endo

ISSN:0899-0042    

DOI:10.1002/chir.530070708

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractA high‐performance liquid chromatography and molecular modelling study is presented for the diastereomeric adducts of a series of chiral thiol compounds and chiral amine compounds after reaction witho‐phthalaldehyde (OPA). It is shown that the possibility of hydrogen bonds forming between the thiol and amino residues in the diastereomeric adducts is an important factor for obtaining good selectivity. The experimental elution orders were explained on the basis of the strength of the interaction between the polar groups of the thiol and amine constituents; it was found that the diastereomeric form having the largest distance between these groups always eluted first. Moreover, within a series of OPA derivatives, the differences between the Boltzmann weighted averages of the distances between the polar groups of the two diastereomers show a good correlation with the experimental selectivities. © 1995 Wiley‐Lis

ISSN:0899-0042    

DOI:10.1002/chir.530070709

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

Abstract2(2‐Bromoethyl)bromobenzene was subjected to microbial oxidation by the whole cells ofPseudomonas putida39/D and JM109(pDTG601) yielding (3R,4S)‐2‐(2‐bromoethyl)‐bromocyclohexa‐1,5‐diene‐3,4‐diol. © 19

ISSN:0899-0042    

DOI:10.1002/chir.530070710

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractAssessing the reactivity of optical antipodes is of central importance in drug research. Using the model of 2‐methoxy‐2‐phenylacetic acid‐4‐nitrophenylester (MPE), the rate of hydrolysis in the presence of β‐cyclodextrin (CD), hydroxyethyl‐ and hydroxypropyl‐β‐CD, as well as methyl‐β‐CD is studied photometrically and by means of HPLC (Chiralcel‐OD‐R‐column). Both β‐CD and hydroxyalkylated‐β‐CD catalyze (−)‐(R)‐enantiomers to a larger extent than (+)‐(S)‐enantiomers, resulting in an enrichment of the latter. Methyl‐β‐CD stabilizes the ester trifold, thus abo

ISSN:0899-0042    

DOI:10.1002/chir.530070711

出版商:Alan R. Liss, Inc.    

年代:1995

数据来源: WILEY