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Diastereomers
Kinds of Diastereomers Selected AbstractsChemInform Abstract: High Regioselectivity in Propylene Hydroformylation Using Rhodium-Bisphosphite Catalysts Is Due to Properties of the SRS Diastereomer.CHEMINFORM, Issue 7 2002John R. Briggs Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Total Synthesis, Characterization, and Conformational Analysis of the Naturally Occurring Hexadecapeptide Integramide,A and a DiastereomerCHEMISTRY - A EUROPEAN JOURNAL, Issue 1 2010Marta De, Zotti Dr. Abstract Integramide,A is a 16-amino acid peptide inhibitor of the enzyme HIV-1 integrase. We have recently reported that the absolute stereochemistries of the dipeptide sequence near the C terminus are L -Iva14 - D -Iva15. Herein, we describe the syntheses of the natural compound and its D -Iva14 - L -Iva15 diastereomer, and the results of their chromatographic/mass spectrometric analyses. We present the conformational analysis of the two compounds and some of their synthetic intermediates of different main-chain length in the crystal state (by X-ray diffraction) and in solvents of different polarities (using circular dichroism, FTIR absorption, and 2D NMR techniques). These data shed light on the mechanism of inhibition of HIV-1 integrase, which is an important target for anti-HIV therapy. [source] Isomer selectivity in aquatic toxicity and biodegradation of bifenthrin and permethrinENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2005Weiping Liu Abstract Synthetic pyrethroids are widely used insecticides, and contamination of surface aquatic ecosystems by pyrethroid residues from runoff is of particular concern because of potential aquatic toxicity. Pyrethroids also are chiral compounds consisting of multiple stereoisomers. In the present study, we evaluated the diastereomer and enantiomer selectivity of cis -bifenthrin (cis -BF) and permethrin (PM) in their aquatic toxicity and biodegradation. The 1R-cis enantiomer was the only enantiomer in cis -BF showing toxicity against Ceriodaphnia dubia. Incubation with pesticide-degrading bacteria showed that the trans diastereomer of PM was selectively degraded over the cis diastereomer, whereas the 1S-cis enantiomer in cis -BF or cis -PM was preferentially degraded over the corresponding 1R-cis enantiomer. The enantioselectivity was significantly greater for cis -PM than for cis -BF and also varied among different strains of bacteria. Isomer selectivity may be a common phenomenon in both aquatic toxicity and biodegradation of pyrethroids, and this should be considered when assessing ecotoxicological risks of these compounds in sensitive ecosystems. [source] Cationic Iridium Complexes with Chiral Dithioether Ligands: Synthesis, Characterisation and Reactivity under Hydrogenation ConditionsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 12 2005Leticia Flores-Santos Abstract A series of cationic IrI complexes containing chiral dithioether ligands have been prepared in order to study the influence of the sulfur substituents and the metallacycle size on the acetamidoacrylate hydrogenation reaction. In the case of complexes 6, 7 and 10, a mixture of diastereomers is observed in solution due to the sulfur inversion processes. In contrast, this fluxional behaviour is efficiently controlled by using bicyclic ligands which inhibit the S-inversion in complexes 8 and 9. The solid-state structure of complex 10b shows only one diastereomer with the sulfur substituents in a relative anti disposition and in an overall configuration of SCSCSSSS at the coordinated dithioether ligand. Iridium complexes containing seven- and six-membered metallacycles (6b,d, 7b,c, 10a,b) react with the substrate through S-ligand substitution, and the rate of this substitution is related to the position of the fluorine atom on the aromatic ring. On the contrary, complexes containing a bismetallacycle (8 and 9) are not displaced by the substrate. The catalytic hydrogenation activity of complexes 8 and 9 is analysed in terms of the high stability of the corresponding dihydride complexes (13 and 14). In both cases, only two of the four possible diastereomeric dihydride species are formed in solution. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] The Effects of Fluorine and Chlorine Substituents across the Fjords of Bifluorenylidenes: Overcrowding and StereochemistryEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2006Sergey Pogodin Abstract The bistricyclic aromatic enes (BAEs) (E)- and (Z)-1,1,-difluorobifluorenylidene, 1,8,1,,8,-tetrafluorobifluorenylidene, (E)- and (Z)-3,3,-difluorobifluorenylidene, 3,6,3,,6,-tetrafluorobifluorenylidene, and their chlorinated analogues were subjected to a DFT study of overcrowding in their fjord regions. The B3LYP hybrid functional was employed to calculate energies and geometries of the twisted conformations of these BAEs. The diastereomers E11,F2 and Z11,F2 have identical twist angles (, = 37.1°) and similar degrees of overcrowding, but differ in the degree and mode of pyramidalization, ,. In E11,F2, ,(C9) = +,(C9,) = 7.0° (syn -pyramidalization), while in Z11,F2, ,(C9) = ,,(C9,) = 1.0° (anti -pyramidalization). By contrast, in E11,Cl2 and Z11,Cl2, , = 40.6° and 42.7°, respectively. Introducing four halogen substituents results in higher twist angles: , = 40.3° in 181,8,F4 and 52.6° in 181,8,Cl4. Surprisingly, Z11,F2 is more stable than E11,F2 (,H298 = ,1.9 kJ/mol), whereas Z11,Cl2 is less stable than E11,Cl2 (,H298 = 2.2 kJ/mol). Both results are consistent with the experimental relative stabilities of these diastereomers. The unexpected stability of Z11,F2 is explained by a combination of steric and electronic effects. Calculations of Coulomb energies for point charge systems of atoms C, F, and H in the fjord regions shows stabilization of the (Z) diastereomer by ,45.5 kJ/mol. The dipole,dipole interactions in the fjord region destabilize Z11,F2 by 6.4 kJ/mol relative to E11,F2. Careful examination of the NMR spectra of E11,F2 and Z11,F2 shows, in the latter, evidence of long-range fluorine,fluorine coupling over seven bonds (11.4 Hz) and carbon,fluorine coupling over six bonds (4.8 Hz).(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Complete Chiral Induction from Enantiopure 1,2-Diamines to Benzophenone-Based Achiral Bisphosphane Ligands in Noyori-Type RuII CatalystsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 16 2006Qing Jing Abstract We report the design and synthesis of a novel class of RuII catalysts (3) composed of achiral benzophenone-based bisphosphane ligands and enantiopure 1,2-diamines for the asymmetric hydrogenation of aryl ketones. The developed catalysts show excellent enantioselectivities (up to 97,% ee) and activities (up to S/C = 10,000) in the hydrogenation of a variety of aromatic ketones.Complete chiral induction from the enantiopure 1,2-diamine to the achiral bisphosphane ligand was observed. The coordination of the C=O moiety in 3 to the cationic RuII center is considered to be of key importance in providing a higher thermodynamic and kinetic rotation barrier for the flexible bisphosphane ligand, resulting in the preferential formation of only one diastereomer, and thus explaining the high enantioselectivity of the catalyst. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Asymmetric Cyclopropanation of Optically Active (1-Diethoxyphosphoryl)vinyl p -Tolyl Sulfoxide with Sulfur Ylides: A Rationale for DiastereoselectivityEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2005Wanda H. Midura Abstract The title sulfoxide (S)-(+)- 1a was found to react with sulfur ylides affording the corresponding cyclopropanes in high yields. With fully deuterated dimethyl(oxo)sulfonium methylide, (CD3)2S(O)CD2, the cyclopropanation reaction occurred in a highly diastereoselective manner producing the cyclopropane 4a - d2 as a major diastereomer in which the newly formed quaternary ,-carbon atom is chiral due to isotopic substitution (CH2 vs. CD2). The diastereomer 4b - d2, having the opposite configuration at the ,-carbon atom, was obtained starting form the 2,2-dideuterio substituted vinyl sulfoxide, (S)-(+)- 1a - d2, and the nondeuterated ylide. The diastereomeric ratio in both reactions was found to be ca. 10:1. The reaction of (S)-(+)- 1a with diphenylsulfonium isopropylide yielded the cyclopropane (+)- 7 as a single diastereomer. X-ray structural studies of the crystalline 1-phosphorylvinyl sulfoxide 9 as well as density functional calculations (B3LYP/6-31G*) on (1-phosphoryl)vinyl sulfoxides revealed the origin of the experimentally observed diastereoselectivities and allowed us to propose a transition state model for the cyclopropanation reaction of chiral 1-phosphorylvinyl sulfoxides. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] 2-Methylisocitrate lyases from the bacterium Escherichia coli and the filamentous fungus Aspergillus nidulansFEBS JOURNAL, Issue 12 2001Characterization, comparison of both enzymes In Escherichia coli and Aspergillus nidulans, propionate is oxidized to pyruvate via the methylcitrate cycle. The last step of this cycle, the cleavage of 2-methylisocitrate to succinate and pyruvate is catalysed by 2-methylisocitrate lyase. The enzymes from both organisms were assayed with chemically synthesized threo -2-methylisocitrate; the erythro -diastereomer was not active. 2-Methylisocitrate lyase from E. coli corresponds to the PrpB protein of the prp operon involved in propionate oxidation. The purified enzyme has a molecular mass of approximately 32 kDa per subunit, which is lower than those of isocitrate lyases from bacterial sources (, 48 kDa). 2-Methylisocitrate lyase from A. nidulans shows an apparent molecular mass of 66 kDa per subunit, almost equal to that of isocitrate lyase of the same organism. Both 2-methylisocitrate lyases have a native homotetrameric structure as identified by size-exclusion chromatography. The enzymes show no measurable activity with isocitrate. Starting from 250 mm pyruvate, 150 mm succinate and 10 µm PrpB, the enzymatically active stereoisomer could be synthesized in 1% yield. As revealed by chiral HPLC, the product consisted of a single enantiomer. This isomer is cleaved by 2-methylisocitrate lyases from A. nidulans and E. coli. The PrpB protein reacted with stoichiometric amounts of 3-bromopyruvate whereby the activity was lost and one amino-acid residue per subunit became modified, most likely a cysteine as shown for isocitrate lyase of E. coli. PrpB exhibits 34% sequence identity with carboxyphosphoenolpyruvate phosphonomutase from Streptomyces hygroscopicus, in which the essential cysteine residue is conserved. [source] New P-ligands: The aromaticity and reactivity of 2,4,6-trialkylphenylphospholesHETEROATOM CHEMISTRY, Issue 2 2005György Keglevich A further member of 2,4,6-trialkyl-phenyl-phos-pholes, the ditertbutylmethylphenyl derivative (1c) was characterized by Bird index and by the sum of angles at the phosphorus atom to describe the flattening of the P-pyramid. Both numbers suggested a slight aromaticity. The reaction of arylphospholes with phosphorus tribromide was extended to phosphole 1c leading this occasion, after further steps, to the mixture of 3- and 2-substituted products (3c-1 and 3c-2, respectively). A triisopropylphenyl-2H -phosphole (4) formed by sigmatropic rearrangement was utilized in the preparation of new 1-phosphanorbornene derivatives, such as sulfide 6 and hemi-oxides 8-1 and 8-2. Further oxidation of the latter species (8-1 and 8-2) led to the decomposition of the dimeric structure (11). 4 could also be trapped by benzaldehyde to afford the oxaphosphanorbornene (10) as one diastereomer. Finally, the reversible formation of 2H -phosphole 4 from 1H -phosphole 1a at 150°C was proved. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:104,222, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20077 [source] Structures and properties of two diastereomeric cyclic sulfites derived from cis -3,4-di- tert -butylthiolane-3,4-diol and thionyl chlorideHETEROATOM CHEMISTRY, Issue 7 2003Sanae Tanaka cis-3,4-Di-tert-butylthiolane-3,4-diol (1) was treated with an equimolar amount of thionyl chloride in the presence of triethylamine or pyridine in several solvents of different polarity to furnish two diastereomeric sulfites 2a and 2b generally in excellent combined yields. Although 2a was consistently formed as the major diastereomer when pyridine was used as the base, 2a and 2b were formed in approximately equal amounts when triethylamine was used as the base in polar solvents. X-ray crystallographic analyses revealed that the SO group of 2a is anti to the thiolane ring and that of 2b syn to the thiolane ring. Density functional theory calculations (B3LYP/6-31G* level) revealed that 2a is less stable than 2b by 1.28 kcal mol,1, although 2a was formed generally as the predominant diastereomer. Spectroscopic data of 2a and 2b are discussed with emphasis on comparison with those obtained by calculations. Treatment of 2a and 2b with m-chloroperbenzoic acid resulted in the oxidation of the divalent sulfur atom of the thiolane ring and not the sulfite sulfur atom. The above oxidations took place exclusively at the syn-side with respect to the tert-butyl groups.© 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:587,595, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10192 [source] DiPAMP's Big Brother "i- Pr-SMS-Phos" Exhibits Exceptional Features Enhancing Rhodium(I)-Catalyzed Hydrogenation of OlefinsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 17 2009Michel Stephan Abstract Switching Knowles DiPAMP's {DiPAMP=1,2-bis[(o -anisyl)(phenyl)phosphino]- ethane} MeO groups with i- PrO ones led to the i- Pr-SMS-Phos {i- Pr-SMS-Phos=1,2-bis[(o -isoprop- oxyphenyl)(phenyl)phosphino]ethane} ligand which displayed a boosted catalyst activity coupled with an enhanced enantioselectivity in the rhodium(I)-catalyzed hydrogenation of a wide-range of representative olefinic substrates (dehydro-,-amido acids, itaconates, acrylates, enamides, enol acetates, ,,,-diarylethylenes, etc). The rhodium(I)-(i- Pr-SMS-Phos) catalytic profile was investigated revealing its structural attributes and robustness, and in contrast to the usual trend, 31P,NMR analysis revealed that its methyl (Z)-,-acetamidocinnamate (MAC) adduct consisted of a reversed diastereomeric ratio of 1.4:1 in favour of the most reactive diastereomer. [source] Highly Efficient and Versatile Phosphine-Phosphoramidite Ligands for Asymmetric HydrogenationADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 5 2009Matthias Eggenstein Abstract A set of novel phosphine-phosphoramidite ligands possessing two elements of chirality have been prepared through a modular synthetic approach. The ligands (11bS)- N -[2-(diphenylphosphino)phenyl]- N -[(S)-1-phenylethyl]dinaphtho[2,1- d:1,,2,- f][1,3,2]dioxaphosphepin-4-amine [(Sa,Sc)- 1a] and (11bR)- N -[2-(diphenylphosphino)phenyl]- N -[(S)-1-(1-naphthyl)ethyl]dinaphtho[2,1- d:1,,2,- f][1,3,2]dioxaphosphepin-4-amine [(Sa,Sc)- 1b] are unique in providing enantioselectivities ,96% ee and ,94% ee, respectively, in mechanistically distinct hydrogenations of CC, CN and CO double bonds in combination with three different transition metals (rhodium, iridium, and ruthenium, respectively). Particularly remarkable are the enantiomeric excesses up to 97% achieved in the iridium-catalyzed hydrogenation of 2-substituted quinolines, where (11bS)- N -[2-(diphenylphosphino)phenyl]- N -[(S)-1-(naphthalen-1-yl)ethyl]-8,9,10,11, 12,13,14,15-octahydrodinaphtho[2,1- d:1,,2,- f][1,3,2]dioxaphosphepin-4-amine [(Sa,Sc)- 2] proved to be the most selective ligand. Substantially lower ees were obtained with the mismatched diastereomer (Ra,Sc)- 1b and with the N -phenyl-substituted ligand 1c, missing a second element of chirality. [source] Addition, elimination, exchange, and epimerization in nitro sulfonesJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2007Charles A. Kingsbury Abstract Three reactions were studied in the diastereomers of 1-(benzenesulfonyl)-2-nitro-1-phenylpropane (1A and 1B) and briefly in related compounds: elimination of the benzenesulfonyl group, epimerization of one diastereomer to the other, and deuterium/hydrogen exchange at the methine group next to nitro in starting material. The two diastereomers showed quite different reactivity. The high melting diasteromer showed rapid elimination and some exchange. The low melting diastereomer (at approximately a half-life) showed extensive epimerization, and elimination to the alkene, but little exchange. There is little effect of aromatic substituents on reaction course. The situation is complicated by re-addition of benzenesulfinate to the alkene. The addition reaction was similar to elimination in agreement with the Principle of Microscopic Reversibility expectations. An electron transfer mechanism for addition is calculated to be comparatively favorable. Copyright © 2007 John Wiley & Sons, Ltd. [source] Diastereomeric differentiation of norbornene amino acid peptides by electrospray ionization tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2009B. Raju A new class of diastereomeric pairs of non-natural amino acid peptides derived from butyloxycarbonyl (Boc-)protected cis- (2S,3R)- and trans- (2S,3S) -, -norbornene amino acids including a monomeric pair have been investigated by electrospray ionization (ESI) tandem mass spectrometry using quadrupole time-of-flight (Q-TOF) and ion-trap mass spectrometers. The protonated cis -BocN- , -nbaa (2S,3R) (1) (,nbaa,=,, -norbornene amino acid) eliminates the Boc group to form [M+H,Boc+H]+, whereas an additional ion [M+H,C4H8]+ is formed from trans -BocN- , -nbaa (2S,3S) (2). Similarly, it is observed that the peptide diastereomers (di-, tri- and tetra-), with cis -BocN- , -nbaa (2S,3R)- at the N-terminus, initially eliminate the Boc group to form [M+H,Boc+H]+ which undergo further fragmentation to give a set of product ions that are different for the peptides with trans -BocN- , -nbaa (2S,3S)- at the N-terminus. Thus the Boc group fragments differently depending on the configuration of the amino acid present at the N-terminus. It is also observed that the peptide bond cleavage in these peptides is less favoured and most of the product ions are formed due to retro-Diels-Alder fragmentation. Interestingly, sodium-cationized peptide diastereomers mainly yield a series of retro-Diels-Alder fragment ions which are different for each diastereomer as they are formed starting from [M+Na,Boc+H]+ in peptides with cis -BocN- , -nbaa (2S,3R)- at the N-terminus, and [M+Na,C4H8]+ in peptides with trans -BocN- , -nbaa (2S,3S)- at the N-terminus. All these results clearly indicate that these diastereomeric pairs of peptides yield characteristic product ions which help distinguish the isomers. Copyright © 2009 John Wiley & Sons, Ltd. [source] Self and nonself recognition of chiral catalysts: The origin of nonlinear effects in the amino-alcohol catalyzed asymmetric addition of diorganozincs to aldehydesTHE CHEMICAL RECORD, Issue 2 2001Ryoji Noyori Abstract Asymmetric addition of dialkylzincs to aldehydes in the presence of (2S)-3- exo -(dimethylamino)isoborneol [(S)-DAIB] exhibits various nonclassical phenomena. The enantiomeric excess (ee) of the alkylation product, obtained with partially resolved DAIB, is much higher than that of the chiral amino alcohol, while the rate decreases considerably as the ee of DAIB is lowered. The asymmetric amplification effects reflect the relative turnover numbers of two enantiomorphic catalytic cycles, where an essential feature is the reversible homochiral and heterochiral dimerization of the coexisting enantiomeric DAIB-based Zn catalysts. The interplay between the thermodynamics of the monomer/dimer equilibration and the kinetics of alkylation reaction strongly affect the overall profile of asymmetric catalysis. The self and nonself recognition of the chiral Zn catalysts is a general phenomenon when (S)-DAIB is mixed with its enantiomer, diastereomer, or even an achiral ,-amino alcohol. The degree of nonlinearity is highly affected not only by the structures and purity of catalysts but also by various reaction parameters. The salient features have been clarified on the basis of molecular weight measurements, NMR and X-ray crystallographic studies of organozinc complexes, and kinetic experiments, as well as computer-aided quantitative analysis. © 2001 John Wiley & Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1:85,100, 2001 [source] gem -Dimethylcyclopropanation of dibenzylideneacetone using triisopropyl sulfoxonium tetrafluoroborateACTA CRYSTALLOGRAPHICA SECTION C, Issue 2 2009Michael G. Edwards The reaction between dibenzylideneacetone (dba) and triisopropyl sulfoxonium tetrafluoroborate has been reinvestigated. The stereochemistry of the major diasteromeric bis(gem -dimethylcyclopropane) adduct has now been assigned as [(1RS,3RS)-2,2-dimethyl-3-phenylcyclopropyl][(1SR,3SR)-2,2-dimethyl-3-phenylcyclopropyl]methanone, C23H26O, by X-ray crystallographic studies on a twinned crystal. The asymmetric unit contains two molecules of the adduct, the conformations of which differ in the orientation of the phenyl ring relative to the adjacent cyclopropanated double bond. The carbonyl groups of each adduct are aligned approximately along the a axis and in opposite directions to each other. The molecules pack to give a sinusoidal pattern along the b axis. This is the first acyclic bis(dimethylcyclopropyl) ketone for which an X-ray crystal structure determination has been reported, and is also the first bis-cyclopropanated dba analogue. The knowledge that the major diastereomer has the meso structure (and therefore the confirmation that the minor isomer is the racemate) will prove invaluable in future studies to utilize bis(dimethylcyclopropyl) ketones as reagents, in rearrangement processes, and as potential ligands and ligand precursors in organometallic chemistry. [source] Total Synthesis, Characterization, and Conformational Analysis of the Naturally Occurring Hexadecapeptide Integramide,A and a DiastereomerCHEMISTRY - A EUROPEAN JOURNAL, Issue 1 2010Marta De, Zotti Dr. Abstract Integramide,A is a 16-amino acid peptide inhibitor of the enzyme HIV-1 integrase. We have recently reported that the absolute stereochemistries of the dipeptide sequence near the C terminus are L -Iva14 - D -Iva15. Herein, we describe the syntheses of the natural compound and its D -Iva14 - L -Iva15 diastereomer, and the results of their chromatographic/mass spectrometric analyses. We present the conformational analysis of the two compounds and some of their synthetic intermediates of different main-chain length in the crystal state (by X-ray diffraction) and in solvents of different polarities (using circular dichroism, FTIR absorption, and 2D NMR techniques). These data shed light on the mechanism of inhibition of HIV-1 integrase, which is an important target for anti-HIV therapy. [source] 1-(,-Aminobenzyl)-2-naphthol: A New Chiral Auxiliary for the Synthesis of Enantiopure ,-Aminophosphonic AcidsCHEMISTRY - A EUROPEAN JOURNAL, Issue 27 2009Kirill Abstract Ooh Betti! A new diastereoselective synthesis of ,-aminophosphonates has been developed based on the reaction of trialkyl phosphites with chiral imines derived from (R)- or (S)-1-(,-aminobenzyl)-2-naphthol (Betti base; see scheme, X=H, CH3, or Br). The reaction proceeds with high diastereoselectivity. Treatment with HCl results in the formation of the desired ,-aminophosphonic acids. A new diastereoselective synthesis of ,-aminophosphonates has been developed, based on the reaction, in the presence of trifluoroacetic acid, of trialkyl phosphites with chiral imines derived from (R)- or (S)-1-(,-aminobenzyl)-2-naphthol. The reaction proceeds at room temperature in toluene with high diastereoselectivity. The major diastereomer can be separated by crystallization from an appropriate solvent. The relative configuration of both chiral centers of the major diastereomer was determined by single-crystal X-ray structure analysis. The desired ,-aminophosphonic acids can be obtained in enantiopure form by treatment of the corresponding diastereomers with HCl. [source] Vinyl Sulfoxides as Stereochemical Controllers in Intermolecular Pauson,Khand Reactions: Applications to the Enantioselective Synthesis of Natural CyclopentanoidsCHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2004Marta Rodríguez Rivero Abstract The use of sulfoxides as chiral auxiliaries in asymmetric intermolecular Pauson,Khand reactions is described. After screening a wide variety of substituents on the sulfur atom in ,,,-unsaturated sulfoxides, the readily available o -(N,N -dimethylamino)phenyl vinyl sulfoxide (1,i) has proved to be highly reactive with substituted terminal alkynes under N -oxide-promoted conditions (CH3CN, 0,°C). In addition, these Pauson,Khand reactions occurred with complete regioselectivity and very high diastereoselectivity (de=86,>96,%, (S,RS) diastereomer). Experimental studies suggest that the high reactivity exhibited by the vinyl sulfoxide 1,i relies on the ability of the amine group to act as a soft ligand on the alkyne dicobalt complex prior to the generation of the cobaltacycle intermediate. On the other hand, both theoretical and experimental studies show that the high stereoselectivity of the process is due to the easy thermodynamic epimerization at the C5 center in the resulting 5-sulfinyl-2-cyclopentenone adducts. When it is taken into account that the known asymmetric intermolecular Pauson,Khand reactions are limited to the use of highly reactive bicyclic alkenes, mainly norbornene and norbornadiene, this novel procedure constitutes the first asymmetric version with unstrained acyclic alkenes. As a demonstration of the synthetic interest of this sulfoxide-based methodology in the enantioselective preparation of stereochemically complex cyclopentanoids, we have developed very short and efficient syntheses of the antibiotic (,)-pentenomycin I and the (,)-aminocyclopentitol moiety of a hopane triterpenoid. Se ha estudiado la utilización de sulfóxidos como auxiliares quirales en reacciones de Pauson,Khand intermoleculares. Tras considerar una amplia variedad de vinil sulfóxidos diferentemente sustituidos en el átomo de azufre, se ha encontrado que el o -(N,N -dimetilamino)fenil sulfóxido (1,i) presenta una elevada reactividad frente a alquinos terminales en reacciones de Pauson,Khand. Además, estas reacciones transcurren con regioselectividades completas y diastereoselectividades muy elevadas (ed=86,>96,%). Estudios teóricos y experimentales sugieren que la gran reactividad mostrada por el vinil sulfóxido 1,i se debe a la capacidad del grupo amino para coordinarse al complejo de dicobalto del alquino, favoreciendo así la posterior formación del cobaltaciclo intermedio. Por otro lado, estudios tanto teóricos como experimentales han demostrado que la elevada diastereoselectividad del proceso es consecuencia de la fácil epimerización termodinámica en la posición C-5 de las 5-sulfinil-2-ciclopentenonas finales. Teniendo en cuenta que hasta el momento la reacción de Pauson,Khand intermolecular estaba limitada al empleo de alquenos bicíclicos muy reactivos, principalmente norborneno y norbornadieno, este nuevo procedimiento constituye la primera versión asimétrica con alquenos acíclicos no tensionados. Como demostración de la utilidad sintética de esta nueva metodología en la preparación enantioselectiva de sistemas ciclopentánicos complejos, se han desarrollado síntesis muy eficaces del antibiótico (,)-pentenomicina I y de la unidad de aminociclopentitol de un triperpenoide. [source] Recent developments in peptide stereoisomer separations by capillary electromigration techniquesELECTROPHORESIS, Issue S1 2009Gerhard K. E. Scriba Abstract The stereochemistry of peptides determines their physicochemical and biological activities. Thus, analytical methods that are able to discriminate between peptide stereoisomers are important. As peptides are typically hydrophilic compounds, many methods for the separation of peptide diastereomers and enantiomers have been developed by capillary electromigration techniques. Moreover, peptide enantiomers displayed unique migration behavior such as a pH-dependent change of the enantiomer migration order in CD-mediated enantioseparations in CE making them ideal compounds to study mechanistic effects of enantioseparations. The present short review summarizes recent developments in the separation of stereoisomers of peptide and peptidomimetics by capillary electromigration techniques. Moreover, recent NMR and molecular modeling studies as well as investigation on the effect of buffer additives on complex formation will be discussed as attempts to understand mechanistic aspects of peptide enantioseparations and to analyze the structure of peptide-CD complexes. [source] Evaluation of carrier ampholyte-based capillary electrophoresis for separation of peptides and peptide mimetics,ELECTROPHORESIS, Issue 18 2008an Koval Abstract Carrier ampholyte-based capillary electrophoresis (CABCE) has recently been introduced as an alternative to CE (CZE) in the classical buffers. In this study, isoelectric BGEs were obtained by fractionation of Servalyt pH 4,9 carrier ampholytes to cuts of typical width of 0.2 pH unit. CABCE feasibility was examined on a series of insect oostatic peptides, i.e. proline-rich di- to decapeptides, and phosphinic pseudopeptides , tetrapeptide mimetics synthesized as a mixture of four diastereomers having the ,P(O)(OH),CH2, moiety embedded into the peptide backbone. With identical selectivity, the separation efficiency of CABCE proved to be as good as classical CE for the insect oostatic peptides and better for diastereomers of the phosphinic pseudopeptides. In addition, despite the numerous species present in the narrow pH cuts of carrier ampholytes, CABCE seems to be free of system zones that could hamper the analysis. Peak symmetry was good for moderately to low mobile peptides, whereas some peak distortion due to electromigration dispersion, was observed for short peptides of rather high mobility. [source] Capillary electrophoresis of amphipathic ,-helical peptide diastereomersELECTROPHORESIS, Issue 1 2004Traian V. Popa Abstract We have made a rigorous assessment of the ability of capillary electrophoresis to resolve peptide diastereomers through its application to the separation of a series of synthetic 18-residue, amphipathic ,-helical monomeric peptide analogues, where a single site in the centre of the hydrophobic face of the ,-helix is substituted by 19 L - or D -amino acids. Such L - and D -peptide pairs have the same mass-to-charge ratio, amino acid sequence and intrinsic hydrophobicity, varying only in the stereochemistry of one residue. CE approaches assessed in their ability to separate diastereomeric peptide pairs included capillary zone electrophoresis (uncoated capillary), micellar electrokinetic chromatography (uncoated capillary in the presence of 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, CHAPS), open-tubular capillary electrochromatography (C8 -coated capillary in the presence of 25% 2,2,2-trifluoroethanol (TFE) or 25% ethanol). Overall, the OT-CEC methods were the most effective at separating the most peptide pairs, particularly for those containing hydrophilic side chains. However, the MEKC approach proved most effective for separation of peptide pairs containing hydrophobic or aromatic side chains. [source] Cationic Iridium Complexes with Chiral Dithioether Ligands: Synthesis, Characterisation and Reactivity under Hydrogenation ConditionsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 12 2005Leticia Flores-Santos Abstract A series of cationic IrI complexes containing chiral dithioether ligands have been prepared in order to study the influence of the sulfur substituents and the metallacycle size on the acetamidoacrylate hydrogenation reaction. In the case of complexes 6, 7 and 10, a mixture of diastereomers is observed in solution due to the sulfur inversion processes. In contrast, this fluxional behaviour is efficiently controlled by using bicyclic ligands which inhibit the S-inversion in complexes 8 and 9. The solid-state structure of complex 10b shows only one diastereomer with the sulfur substituents in a relative anti disposition and in an overall configuration of SCSCSSSS at the coordinated dithioether ligand. Iridium complexes containing seven- and six-membered metallacycles (6b,d, 7b,c, 10a,b) react with the substrate through S-ligand substitution, and the rate of this substitution is related to the position of the fluorine atom on the aromatic ring. On the contrary, complexes containing a bismetallacycle (8 and 9) are not displaced by the substrate. The catalytic hydrogenation activity of complexes 8 and 9 is analysed in terms of the high stability of the corresponding dihydride complexes (13 and 14). In both cases, only two of the four possible diastereomeric dihydride species are formed in solution. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Synthesis of New ,-(Polyfluoroalkyl)-,-hydroxy-,-amino AcidsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 29 2009Nataliya A. Tolmacheva Abstract New ,-(polyfluoroalkyl)-,-hydroxy-,-amino acids were synthesized from the corresponding starting 3-(benzoylamino)-6-(polyfluoroalkyl)-2H -pyran-2-ones. The key step of the synthesis was the hydrogenation of the pyrone ring. Stereoselectivity and yields depended dramatically on the reaction conditions and the nature of the polyfluoroalkyl group. Various conditions were used for the preparation of both mixtures of diastereomers and pure diastereomers of the target amino acids. The obtained ,-(polyfluoroalkyl)-,-hydroxy-,-amino acids are of interest as analogues of 2-amino-5-hydroxyvaleric acid and glutamic acid.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Synthesis of Tyrosine-Derived Tetrahydroisoquinolines by Lewis Acid Catalyzed Cyclization of N -(Phenylsulfonyl)alkyloxazolidinones,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 33 2007Stefan Tussetschläger Abstract N -Boc-protected tyrosine esters 5a,b were converted into tetrahydroisoquinolines 13 and 14 in four steps by reduction and ring closure to oxazolidinones 9 and 10, addition of benzenesulfinic acid and aldehydes to sulfones 11 and 12 and subsequent Lewis acid catalyzed cyclization. In the case of m -tyrosine derivative 5a, selective protection with bromine prevented the formation of undesired regioisomers. Debromination of target compounds 13 was readily achieved under radical reduction conditions by using Bu3SnH/AIBN. Tetrahydroisoquinolines 13 and 14 were isolated as single diastereomers whose trans configuration was confirmed by X-ray crystal structure analysis. Partial epimerization of trans - 13i and trans - 21 to the corresponding cis diastereomers was achieved under basic conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Short Synthesis of Orthogonally Protected 3,,12,-Diamino-5,-cholan-24-oic Acid, a Dipodal Steroid Scaffold for Combinatorial ChemistryEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2007Dieter Verzele Abstract A short, practical, multigram-scale synthesis of C3,-NHAlloc, C12,-NHBoc-diamino-5,-cholan-24-oic acid 2 was developed, applying a new, straightforward synthetic strategy. Key features are the conservation of the carboxyl moiety at C24 during oxime reduction, the late differentiation between the C3 and C12 amino groups and the gradual separation of diastereomers during the synthesis. This orthogonally protected diamino steroid derivative can be used as starting point for the generation of steroid based dipodal peptide and non-peptide combinatorial libraries. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Synthesis of Both Enantiomers of Conduritol C Tetraacetate and of meso -Conduritol D Tetraacetate by Oxidation of Benzoquinone Bis(ethylene acetal)EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2007Martin Lang Abstract Epoxidation of p -benzoquinone bis(ethylene acetal) (1) with m -chloroperbenzoic acid or hydrogen peroxide/benzonitrile afforded corresponding monoepoxide 2, which was converted into p -benzoquinone mono(ethylene acetal) monoepoxide 5 with perchloric acid. Dihydroxylation of 1 with osmium tetroxide or ruthenium trichloride/sodium periodate afforded corresponding cis -diol 6, which was subsequently acetylated to give diacetate 7. One ethyleneacetal moiety in 7 could be selectively hydrolyzed with silica gel/ferric chloride under solvent-free conditions to give ketone 8, which, upon reduction with sodium borohydride and subsequent acetylation of the formed alcohol group, afforded two diastereomeric triacetates 10. Hydrolysis of the remaining acetal functions in the two diastereomers 10, followed by reduction of the second carbonyl group as described above, afforded racemic conduritol C and meso -conduritol D tetraacetates 12 and 13, respectively. Enzymatic resolution of the racemic arabino -configured triacetate 10 with Lipozym failed, while the ribo -configured counterpart reacted smoothly to give enantiomerically pure D - ribo - and L - ribo -configured triacetates 10. The latter pair of enantiomerically pure triacetates were converted into both enantiomers of conduritol C tetraacetate 13 as described for the racemic compounds. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Synthesis of an Enantiomerically Pure Building Block for the Synthesis of Hydroporphyrins,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2007Genevieve Etornam Adukpo Abstract The enantiomerically pure pyrrolidine diester 4 is a useful building block for the synthesis of chiral hydroporphyrin compounds. Treatment of optically active aromatic amines with bislactone 5 gave pairs of N -alkylated lactam-lactone diastereomers 6 and 8. These diastereomers were separated by MPL chromatography and in the case of 8 they could be debenzylated to yield the enantiomerically pure lactam-lactone 7 and its enantiomer. The (,)-lactam-lactone enantiomer 7 was further transformed into building block 4.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] The Effects of Fluorine and Chlorine Substituents across the Fjords of Bifluorenylidenes: Overcrowding and StereochemistryEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2006Sergey Pogodin Abstract The bistricyclic aromatic enes (BAEs) (E)- and (Z)-1,1,-difluorobifluorenylidene, 1,8,1,,8,-tetrafluorobifluorenylidene, (E)- and (Z)-3,3,-difluorobifluorenylidene, 3,6,3,,6,-tetrafluorobifluorenylidene, and their chlorinated analogues were subjected to a DFT study of overcrowding in their fjord regions. The B3LYP hybrid functional was employed to calculate energies and geometries of the twisted conformations of these BAEs. The diastereomers E11,F2 and Z11,F2 have identical twist angles (, = 37.1°) and similar degrees of overcrowding, but differ in the degree and mode of pyramidalization, ,. In E11,F2, ,(C9) = +,(C9,) = 7.0° (syn -pyramidalization), while in Z11,F2, ,(C9) = ,,(C9,) = 1.0° (anti -pyramidalization). By contrast, in E11,Cl2 and Z11,Cl2, , = 40.6° and 42.7°, respectively. Introducing four halogen substituents results in higher twist angles: , = 40.3° in 181,8,F4 and 52.6° in 181,8,Cl4. Surprisingly, Z11,F2 is more stable than E11,F2 (,H298 = ,1.9 kJ/mol), whereas Z11,Cl2 is less stable than E11,Cl2 (,H298 = 2.2 kJ/mol). Both results are consistent with the experimental relative stabilities of these diastereomers. The unexpected stability of Z11,F2 is explained by a combination of steric and electronic effects. Calculations of Coulomb energies for point charge systems of atoms C, F, and H in the fjord regions shows stabilization of the (Z) diastereomer by ,45.5 kJ/mol. The dipole,dipole interactions in the fjord region destabilize Z11,F2 by 6.4 kJ/mol relative to E11,F2. Careful examination of the NMR spectra of E11,F2 and Z11,F2 shows, in the latter, evidence of long-range fluorine,fluorine coupling over seven bonds (11.4 Hz) and carbon,fluorine coupling over six bonds (4.8 Hz).(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Mannich and O -Alkylation Reactions of Tetraalkoxyresorcin[4]arenes , The Use of Some Products in Ligand-Assisted ReactionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2006Benjamin R. Buckley Abstract The measurement of the pKa of racemic tetramethoxyresorcin[4]arenes explains the failure to obtain good yields in attempted Mannich reactions of these substrates under classical reaction conditions. The failure is related to the lack of adequate concentrations of the iminium ions that results from the reduced acid strength of tetraalkoxyresorcin[4]arenes compared with that of the parent octahydroxyresorcin[4]arenes. However, the preparation of a series of Mannich bases derived from racemic tetraalkoxyresorcin[4]arenes was accomplished under microwave-assisted aprotic reaction conditions and the use of preformed iminium ion intermediates. When the reactions were carried out with the use of chiral bis(aminol) ethers, mixtures of diastereomers were obtained that could be separated by flash chromatography. The absolute configurations of the enantiomerically pure tetrabenzoxazine derivatives were established in some cases by X-ray crystallographic analysis and by a comparison of the nuclear magnetic resonance spectroscopic data. The alkylation of racemic tetramethoxyresorcin[4]arenes was achieved with the use of an excess of 2-bromo- N -[(R)-(+)-(,-methylbenzyl)]acetamide in acetonitrile containing potassium carbonate. Enantioselective ligand-assisted reactions of aromatic aldehydes are also reported with the use of dialkylzinc reagents both in the absence and in the presence of terminal alkynes.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] | |||||||||||||||||||||||||||||||