Diastereoisomeric Pairs Research Articles

Chemistry of novel compounds with multifunctional carbon structure. Part 4. Steric and electronic influences on the diastereoisomeric chemical shift differences in 19F n.m.r. spectra by introduction of fluorine, phenyl, and heteroatom groups into acetates

In order to develop reagents more efficient than MTPA for the determination of enantiomeric excess, several fluoroacetic esters (2b)–(7b) have been prepared which have various heteroatom-centred groups or bulky groups at the α position. These compounds have been converted into the corresponding s-butyl ester (8a)–(13a), α-phenylethyl ester (8b)–(13b), and α-phenylethylamide (8c)–(13c) diastereoisomers; the chemical shift differences between each pair of diastereoisomers (Δδ) have been obtained from the 1H and 19F n.m.r. spectra for each derivative. The influence on Δδ values of steric and possible electronic effects which arise upon introduction of a phenyl or a heteroatom group into the fluoroacetate structure are discussed.

Evaluation of the Binding to Fixed Platelets of Agonists and Antagonists of ADP-Induced Aggregation

Steady state binding of eleven different ADP analogues to formaldehyde-fixed platelets has been determined in a competitive binding assay using 3H-ADP. The compounds tested were the inactive analogues L-ADP and L-ATP; the agonists 2-chloroadenosine 5'-diphosphate, adenosine 5'-O-(2-thiodiphosphate) and the diasteroisomeric pair Sp-adenosine 5'-(1-thiodiphosphate) (Sp-ADP-alpha-S) and Rp-adenosine 5'-(1-thiodiphosphate) (Rp-ADP-alpha-S); and the antagonists adenosine 5'-O-thiomonophosphate, 2-chloroadenosine 5'-O-thiomonophosphate, 2-choloroadenosine 5'-triphosphate, and the diastereoisomeric pair 5'-(1-thiotriphosphate) (Sp-ATP-alpha-S) and RP-adenosine 5'-(1-thiotriphosphate) (Rp-ATP-alpha-S). All compounds tested competed at the high affinity binding sites for ADP previously identified (Blood 1988; 71: 110-6) but in some cases competition could not be demonstrated at the low affinity sites because of the high nucleotide concentrations required. As a group, C2-substituted analogues bound less strongly (Ki greater than 2 micro M) than did the analogues without substituents in the purine ring (Ki less than 0.7 microM). With the pair of diastereoisomeric agonists Sp-ADP-alpha-S and Rp-ADP-alpha-S the Ki values at the high affinity site (210 nM and 560 nM) were of the same relative magnitude and in the same direction as their reported potencies as agonists (Ki 4 microM and 20 microM). With the diastereoisomeric antagonists Sp-ATP-alpha-S and Rp-ATP-alpha-S a similar relationship was seen between affinity (17 nM and 156 nM) and inhibitory potency (Ki 4 microM and 20 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives

The preparation and acid catalysed hydrolysis of a number of isoxazolinyldioxepins is reported. Individual diastereoisomer pairs were isolated by column chromatography and shown to differ significantly in their hydrolytic stability at acidic pH. The crystal structures of one diastereoisomer pair reveal that conformational differences induce a selective stereoelectronic effect at the acetal centre of the more hydrolytically labile isomer, while the less labile isomer shows no such selectivity.

Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives

The preparation and acid catalysed hydrolysis of a number of isoxazolinyldioxepins is reported. Individual diastereoisomer pairs were isolated by column chromatography and shown to differ significantly in their hydrolytic stability at acidic pH. The crystal structures of one diastereoisomer pair reveal that conformational differences induce a selective stereoelectronic effect at the acetal centre of the more hydrolytically labile isomer, while the less labile isomer shows no such selectivity.

High-performance liquid chromatographic method for the simultaneous determination of the enantiomers of carvedilol and its O-desmethyl metabolite in human plasma after chiral derivatization

High-performance liquid chromatographic method for the simultaneous determination of the enantiomers of carvedilol and its O-desmethyl metabolite in human plasma after chiral derivatization

Stereochemical influences upon the opioid ligand activities of 4‐alkyl‐4‐arylpiperidine derivatives

The synthesis and stereochemistry (configuration and preferred solute conformation) of some 4-alkyl (methyl, n-propyl, isobutyl)-4-(3-hydroxy-phenyl)-1-methylpiperidines and corresponding 3-methyl diastereoisomeric pairs are reported, together with their in vivo and in vitro activities as opioid ligands. All potent agonists exhibit a preference for axial 4-aryl chair conformations when protonated, and stereochemical analogies with rigid opioids of the benzomorphan class are discussed. Antagonist properties are found in compounds with preference for equatorial 4-aryl chairs, notably the cis 3,4-dimethyl derivative.

Asymmetric Diels-Alder cycloadditions with acylnitroso dienophiles obtained from L-proline

Asymmetric Diels-Alder cycloadditions with acylnitroso dienophiles obtained from L-proline

Resolution of chiral interconvertible diastereoisomers of a 2,18-bridged biliverdin mediated by first-order asymmetric transformation

Chiral diastereoisomers of the bridged biliverdin 2,18-(1′,4′-dimethoxybutane-1′,4′-diyl)-8,12-bis(2″-methoxycarbonylethyl)-3,7,13,17-tetramethylbilin-1,19-(21H,24H)-dionerac-(1a) and rac-(1b) have been resolved and isolated from the four-component mixture. Repetitive enrichment of M-helical isomers with (R)-(–)-mandelic acid followed by chromatographic separation afforded one enantiomer of each diastereoisomeric pair, viz. (M-SS)-(1a) and (M-RR)-(1b). The corresponding enantiomorphic species (P-RR)-(1a) and (P-SS)-(1b) were each obtained from their respective diastereoisomeric counterpart by thermal conversion. The enantiomeric purities achieved (>95%) were checked by n.m.r. techniques. The rotational strengths R(absolute values) of the visible c.d. bands exhibited by the diastereoisomers of (1) are close to one another and similar to those reported for open-chain bilatrienes. The influence of chirality centres on helical excess (h.e.) and helicity of the bridged bilatriene moiety and its pronounced solvent dependence is discussed.

Synthesis and stereochemistry of a helical 2,18-bridged biliverdin

Biliverdin-IIIα dimethyl ester (1) when treated with acidic methanol undergoes ring closure of the exocyclic vinyl groups with consecutive addition of two methoxy groups and oxidation, predominantly affording (3). The four-membered bridge connecting the pyrrolinone rings possesses two chiral centres of equal configuration either (1′R,4′R) or (1′S,4′S). Due to the M/P helicity of the bilatriene backbone, (3) comprises two thermally interconvertible diastereoisomeric pairs of enantiomers, viz. (3a) of configuration [(P,1′R,4′R) and (M,1′S,4′S)] and (3b) of configuration [(M,1′R,4′R) and (P,1′S,4′S)]. Their stereochemistry was assigned by n.m.r. techniques. The flexibility of the bilatriene unit is restricted so the separation of (3a) and (3b) can be seen at moderately low temperatures. Despite geometric contraints the torsional angles of the bilatriene backbones are close to non-bridged helical shaped derivatives. A mechanism for the acid mediated cyclisation reaction is proposed and briefly discussed.

Studien zur CH-Aktivierung: IV. Inter- und Intra-molekulare CH-Aktivierung mit Komplexfragmenten des Typs [C 6R 6M(L)] (M = Ru, Os)

Studien zur CH-Aktivierung: IV. Inter- und Intra-molekulare CH-Aktivierung mit Komplexfragmenten des Typs [C 6R 6M(L)] (M = Ru, Os)

Soman-hydrolyzing and -detoxifying properties of an enzyme from a thermophilic bacterium

Soman-hydrolyzing and -detoxifying properties of an enzyme from a thermophilic bacterium

Synthesis of pseudo-trehaloses: [(1,2, [formula omitted],5)-2,3,4-trihydroxy-5-hydroxymethyl-1-cyclohexyl] d-glucopyranosides

Synthesis of pseudo-trehaloses: [(1,2, [formula omitted],5)-2,3,4-trihydroxy-5-hydroxymethyl-1-cyclohexyl] d-glucopyranosides

Non‐covalent interactions in the protonation of diastereoisomeric dipeptides in aqueous solution

New and already reported thermodynamic data concerning the protonation of a series of diastereoisomeric pairs of dipeptides have been compared with the upfield chemical shifts observed in the PMR spectra of some systems as a consequence of alkyl‐aryl interactions. The enthalpy and entropy changes associated with the protonation of the dipeptides, obtained by potentiometric and calorimetric measurements, together with the PMR data, show the importance of the solvophobic and the electrostatic interactions in the stereoselectivity of these systems. The overall agreement and the differences are discussed.

Molecular mechanics of diastereoisomers with phenyl groups on neighbouring carbon atoms

Molecular mechanics of diastereoisomers with phenyl groups on neighbouring carbon atoms

NMR SPECTRA AND STEREOCHEMISTRY OF DIASTEREOISOMERIC 4,5-DIPHENYL-CYCLOPHOSPHAMIDES

Abstract The conformational distribution and relative configuration of four diastereoisomeric pairs of 4,5-diphenyl-cyclophosphamides and their N-methyl analogues were determined by means of 1H, 13C, 31P NMR and IR spectroscopy.

Intramolekulare Cycloadditionen Mit Azomethin‐Yliden: Synthese und NMR‐Untersuchungen einiger Paracyclophan‐Derivate vom Makrolid‐Typ

Intramolecular Cycloaddition Reactions with Azomethine Ylides: Synthesis and NMR Investigations of Some Macrolide‐Type ParacyclophanesSeveral aziridine derivatives bearing a para‐substituted phenyl group have been prepared as precursors of azomethine ylides for intramolecular 1,3‐dipolar cycloadditions. Upon heating in refluxing toluene, the expected reactions take place resulting in the regioselective formations of the pairs of diastereoisomers 14/15 and 16/17, respectively. As indicated by the sharply decreasing yield in the a‐series (< 5%), a useful application of this method for preparing paracyclophane compounds is restricted to derivatives with more than 11 bridging atoms. The results of detailed 1H‐ and 13C‐NMR investigations with the pyrrolidino‐annulated cyclophanes are discussed with respect to the configuration at the five‐membered heterocycles and to the conformational flexibility of the bridges.

Carboxylic acids as indicators of oil migration—I. Occurrence and geochemical significance of C-22 diastereoisomers of the (17βH,21βH) C 30 hopanoic acid in geological samples

Carboxylic acids as indicators of oil migration—I. Occurrence and geochemical significance of C-22 diastereoisomers of the (17βH,21βH) C 30 hopanoic acid in geological samples

Soman-Hydrolyzing and -Detoxifying Properties of an Enzyme from a Thermophilic Bacterium

Soman-Hydrolyzing and -Detoxifying Properties of an Enzyme from a Thermophilic Bacterium. Chettur, G., DeFrank, J. J., Gallo, B. J., Hoskin, F. C. G., Mainer, S., Robbins, F. M., Steinmann, K. E., and Walker, J. E. (1988). Fundam. Appl. Toxicol 11, 373-380. An enzyme that hydrolyzes soman (1,2,2-trimethylpropyl methylphosphonofluoridate) and two other phosphonofluoridates, but does not hydrolyze DFP (diisopropylphosphorofluoridate), has been partially purified from a rod-shaped spore-forming gram-positive OT (obligate thermophilic) bacterium. The enzyme shows a marked Mn 2+ stimulation, and in this and its substrate preference does not resemble the organophosphorus acid anhydrolase (sometimes termed DFPase) found in squid. Like the squid enzyme, it is not inhibited by mipafox (N. N‘-diisopropyl-phosphordiamidofluoridate), is not inactivated by ammonium sulfate, and does hydrolyze the acetylcholinesterase-inhibitory pair of diastereoisomers of soman as well as the relatively nonin-hibitory pair, thus detoxifying soman. In these three properties the OT enzyme does not resemble the ubiquitous organophosphorus acid anhydrolase often purified from mammalian and bacterial sources by cold ethanol fractionation. Thus this phosphono-specific OT enzyme may have a natural substrate and a physiological role distinct from other organophosphorus acid anhydrolases.

Asymmetric synthesis of labelled amino acids, part V:The preparation of L-3-(3,4-dimethoxyphenyl)alanine-[3- 14C] and the total synthesis of labelled ace inhibitor RS-10085 in high optical purity

Asymmetric synthesis of labelled amino acids, part V:The preparation of L-3-(3,4-dimethoxyphenyl)alanine-[3- 14C] and the total synthesis of labelled ace inhibitor RS-10085 in high optical purity

Chromatographic behaviour of diastereoisomers : IX. Application of a microcomputer program to the thin-layer chromatographic separation of some diastereoisomers on silica

Chromatographic behaviour of diastereoisomers : IX. Application of a microcomputer program to the thin-layer chromatographic separation of some diastereoisomers on silica