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Enantiomerically Pure (enantiomerically + pure)
Selected AbstractsSynthesis of Enantiomerically Pure 2,3,4,6-Tetrasubstituted Tetrahydropyrans by Prins-Type Cyclization of Methyl Ricinoleate and Aldehydes,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2006Ursula Biermann Abstract The AlCl3 -catalyzed Prins-type cyclization of methyl ricinoleate (1), an enantiomerically pure renewable compound, with aldehydes such as heptanal (2a), isobutyraldehyde (2b), pivaldehyde (2c) and benzaldehyde (2d) is a simple reaction for the diastereoselective synthesis of enantiomerically pure 2,3,6-trialkyl-substituted 4-chlorotetrahydropyrans. The respective 4-hydroxytetrahydropyrans are obtained e.g. with aldehydes 2a and 2d using montmorillonite KSF/O as the catalyst. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Synthesis and Conformational Analysis of Pentapeptides Containing Enantiomerically Pure 2,2-Disubstituted GlycinesHELVETICA CHIMICA ACTA, Issue 3 2008Kathrin Abstract The synthesis and conformational analysis of model pentapeptides with the sequence Z-Leu-Aib-Xaa-Gln-Valol is described. These peptides contain two 2,2-disubstituted glycines (,,, -disubstituted , -amino acids), i.e., Aib (aminoisobutyric acid), and a series of unsymmetrically substituted, enantiomerically pure amino acids Xaa. These disubstituted amino acids were incorporated into the model peptides via the ,azirine/oxazolone method'. Conformational analysis was performed in solution by means of NMR techniques and, in the solid state, by X-ray crystallography. Both methods show that the backbones of these model peptides adopt helical conformations, as expected for 2,2-disubstitued glycine-containing peptides. [source] Synthesis of Enantiomerically Pure 1,5,5-Trideuterated cis- and trans -2,4-Dioxa-3-phosphadecalins. 31P-NMR Evidence of Covalent-Bond Formation and the Stereochemical Implications in the Course of the Inhibition of , -ChymotrypsinHELVETICA CHIMICA ACTA, Issue 11 2007Markus Abstract The irreversible inhibition of , -chymotrypsin with the enantiomerically pure, P(3)-axially and P(3)-equatorially X-substituted cis- and trans- configurated 2,4-dioxa-3-phospha(1,5,5- 2H3)bicyclo[4.4.0]decane 3-oxides (X=F, 2,4-dinitrophenoxy) was monitored by 31P-NMR spectroscopy. 1H-Correlated 31P{2H}-NMR spectra enabled the direct observation of the vicinal coupling (3J) between the P-atom of the inhibitor and the CH2O moiety of Ser195 (=,Ser195'(CH2O)), thus establishing the covalent nature of the ,Ser195'(CH2OP) bond in the inhibited enzyme. The stereochemical course of the phosphorylation is dependent on the structure of the inhibitor, and neat inversion, both inversion and retention, as well as neat retention of the configuration at the P-atom was found. [source] A Convenient Preparation of Enantiomerically Pure (+)-(1R,2R)- and (,)-(1S,2S)-1,2-Diamino-1,2-diphenylethanesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 7-8 2006Christopher Braddock Abstract A gram-scale preparation of (1S,2S)- and (1R,2R)-1,2-diamino-1,2-diphenylethanes, (1S,2S)- 1 and (1R,2R)- 1, is reported via (±)- iso -amarine 4. Strategically, the activation of (±)- iso -amarine 4 for hydrolysis to the required diamines and enantiomeric resolution is achieved simultaneously by formation of two separable diastereoisomeric N -acylamidines 5 and 6 derived from direct DCC-mediated coupling of (±)- iso -amarine 4 with (R)-acetylmandelic acid. iso -Amarine 4 is conveniently obtained from amarine 3, and a one-pot synthesis of the latter is reported from benzaldehyde and hexamethyldisilazane as catalysed by benzoic acid. [source] ChemInform Abstract: A Large-Scale Synthesis of Enantiomerically Pure ,-Hydroxyorganochalcogenides.CHEMINFORM, Issue 23 2010Jefferson L. Princival 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] Enantiomerically Pure 1,4-Benzodiazepine-2,5-diones as Hdm2 Antagonists.CHEMINFORM, Issue 37 2006Juan Jose Marugan Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Highly Functionalized Organolithium and Organoboron Reagents for the Preparation of Enantiomerically Pure ,-Amino Acids.CHEMINFORM, Issue 31 2005Christopher W. Barfoot Abstract For Abstract see ChemInform Abstract in Full Text. [source] Chemoenzymatic Synthesis of Enantiomerically Pure 1,2-Diols Employing Immobilized Lipase in the Ionic Liquid [bmim]PF6.CHEMINFORM, Issue 9 2005Ahmed Kamal Abstract For Abstract see ChemInform Abstract in Full Text. [source] Diastereoselective Aldol Reactions of Furaldehyde Using a Chiral Boronate as Auxiliary: Application to the Synthesis of Enantiomerically Pure and Highly Functionalized 2,3-Disubstituted Furanyl Alcohols.CHEMINFORM, Issue 19 2003Kin-Fai Chan Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: Diastereoselective Synthesis of Enantiomerically Pure 1,2-Disubstituted Cyclopropanols from Allylic Sulfones.CHEMINFORM, Issue 25 2002D. Diez 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] ChemInform Abstract: Efficient Chemoenzymatic Synthesis of Enantiomerically Pure ,-Heterocyclic Amino Acid Derivatives.CHEMINFORM, Issue 20 2001Valerie Rolland-Fulcrand 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] Synthesis of Enantiomerically Pure 1,2,3,4-Tetrahydro-,-carbolines and N -Acyl-1-aryl Ethylamines by Rhodium-Catalyzed HydrogenationCHEMISTRY - AN ASIAN JOURNAL, Issue 7 2008Stephan Enthaler Dr. Abstract The rhodium-catalyzed asymmetric hydrogenation of different enamides, in particular, dihydro-,-carboline derivates, was investigated in the presence of chiral phosphorus ligands. Enantioselectivities of up to 99,%,ee were obtained after ligand screening and optimization of the reaction conditions. The scope and limitation of the catalysts were shown in the synthesis of optically active tetrahydro-,-carbolines and other benchmark N -acyl-1-aryl ethylamines. Im Rahmen dieser Arbeit wird die Rhodium-katalysierte asymmetrische Hydrierung von Enamiden vorgestellt, wobei ein besonderes Augenmerk auf der Synthese von Vorstufen für Indolalkaloide (1,2,3,4-Tetrahydro-,-carboline) lag. Nach Untersuchung verschiedenster Ligandensysteme und Optimierung der Reaktionsbedingungen konnten Enantioselektivitäten von bis zu 99,%,ee erzielt werden. Dabei erwiesen sich Phospholan-basierte Diphosphane als besonders geeignet zum Chiralitätstransfer. Die hervorragenden Eigenschaften dieser Ligandklasse konnte weiterhin in der asymmetrischen Hydrierung verschiedenster Enamide erfolgreich gezeigt werden. [source] Synthesis and Cytotoxicity of Enantiomerically Pure [1,2-Diamino-1-(4-fluorophenyl)-3-methylbutane]platinum(II) ComplexesCHEMMEDCHEM, Issue 6 2006Anja Dullin Abstract A series of leaving group derivatives of enantiomerically pure [1,2-diamino-1-(4-fluorophenyl)-3-methylbutane]platinum(II) complexes were synthesized and tested for cytotoxicity. The enantiomeric purity was determined by 1H,NMR spectroscopy on the final diamines after derivation with (1R)-myrtenal. For coordination to platinum, the diamines were reacted with K2PtI4. The treatment of diiodoplatinum(II) complexes (4F-Ph/iProp-PtI2) with Ag2SO4 resulted in the sulfatoplatinum(II) complexes (4F-Ph/iProp-PtSO4), which can be easily transformed to dichloroplatinum(II) complexes (4F-Ph/iProp-PtCl2) with 2,n HCl. The importance of the leaving groups and the configuration at the diamine ligand on the antiproliferative effects was evaluated on the hormone-dependent MCF-7 and the hormone-independent MDA-MB 231 breast cancer cell lines as well as the LNCaP/FGC prostate cancer cell line. (R,R)-4F-Ph/iProp-PtCl2 was identified as the most active platinum(II) complex. The 3-methyl group increased antiproliferative effects relative to the [1,2-diamino-1-(4-fluorophenyl)butane]platinum(II) complexes described in an earlier study. [source] Enantioselective Synthesis of 4-(Dimethylamino)pyridines through a Chemical Oxidation-Enzymatic Reduction Sequence.ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 18 2006Application in Asymmetric Catalysis Abstract Enantiomerically pure 4-(dimethylamino)-3-(1-hydroxyalkyl)pyridines and 4-(dimethylamino)-3-[hydroxy(phenyl)methyl]pyridine have been prepared through efficient chemoenzymatic routes. For this purpose different lipases and oxidoreductases have been tested in the preparation of optically active 4-chloro derivatives and baker's yeast was found to be an excellent catalyst for the bioreductions of the corresponding ketones. Their applications as enantioselective nucleophilic catalysts have been studied, important catalytic properties were observed in the stereoselective construction of quaternary centers. [source] Mixed Aromatic Acyloin Condensations with Recombinant Benzaldehyde Lyase: Synthesis of ,-Hydroxydihydrochalcones and Related ,-Hydroxy KetonesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 6-7 2003Monica Sanchez-Gonzalez Abstract Recombinant benzaldehyde lyase (BAL), expressed and purified from E.,coli strain JM-109, was used to catalyze the condensation of a series of methoxybenzaldehydes and phenylacetaldehyde in the synthesis of ,-(R)-hydroxydihydrochalcones. Enantiomerically pure 1-hydroxy-1,3-diphenylpropan-2-ones and o -anisoin were also obtained as products of the BAL reaction. The R absolute configurations of chiral centers were determined by CD spectroscopy. ,-(R)-Hydroxydihydrochalcones and 1-hydroxy-1,3-diphenylpropan-2-ones are valuable synthons for chemoenzymatic syntheses of flavonoids. This is the first synthesis of ,-(R)-hydroxydihydrochalcones by a microbial enzyme. [source] Enantiospecific Syntheses of Copper Cubanes, Double-Stranded Copper/Palladium Helicates, and a (Dilithium),Dinickel Coronate from Enantiomerically Pure Bis-1,3-diketones,Solid-State Self-Organization Towards Wirelike Copper/Palladium Strands,CHEMISTRY - A EUROPEAN JOURNAL, Issue 5 2008Abstract Enantiomerically pure, vicinal diols 1 afforded in a two-step synthesis (etherification and subsequent Claisen condensation) chiral bis-1,3-diketones H2L(S,S) (3,a,c) with different substitution patterns. Reaction of these C2 -symmetric ligands with various transition-metal acetates in the presence of alkali ions generated distinct polynuclear aggregates 4,8 by diastereoselective self-assembly. Starting from copper(II) acetate monohydrate and depending on the ratio of transition-metal ion to alkali ion to ligand, chiral tetranuclear copper(II) cubanes (C,C,C,C)-[Cu4(L(S,S))2(OMe)4] (4,a,c) or dinuclear copper(II) helicates (P)-[Cu2(L(S,S))2] (5) could be synthesized with square-pyramidal and square-planar coordination geometry at the metal center. In analogy to the last case, with palladium(II) acetate double-stranded helical systems (P)-[Pd2(L(S,S))2] (6,7) were accessible exhibiting a linear self-organization of ligand-isolated palladium filaments in the solid state with short inter- and intramolecular metal distances. Finally, the introduction of hexacoordinate nickel(II) in combination with lithium hydroxide monohydrate and chiral ligand H2L(S,S) (3,a) allowed the isolation of enantiomerically pure dinuclear nickel(II) coronate [(Li,MeOH)2,{(,,,)-Ni2(L(S,S))2(OMe)2}] (8) with two lithium ions in the voids, defined by the oxygen donors in the ligand backbone. The high diastereoselectivity, induced by the chiral ligands, during the self-assembly process in the systems 4,8 could be exemplarily proven by circular dichroism spectroscopy for the synthesized enantiomers of the chiral copper(II) cubane 4,a and palladium(II) helicate 6. [source] Ring-Closure Reactions through Intramolecular Displacement of the Phenylselenonyl Group by Nitrogen Nucleophiles: A New Stereospecific Synthesis of N -Tosyl and N -Benzoyl-1,3-oxazolidin-2-ones from ,-Hydroxyalkyl Phenyl SelenidesCHEMISTRY - A EUROPEAN JOURNAL, Issue 7 2004Marcello Tiecco Prof. Abstract A new and convenient method for the stereospecific synthesis of variously substituted 1,3-oxazolidin-2-ones from the easily available ,-hydroxyalkyl phenyl selenides is presented. After transformation into the N -tosyl or N -benzoyl carbamates, the selenides were oxidized to the corresponding selenones. The key step of the process is the ring-closure reaction, which occurs by stereospecific intramolecular nucleophilic substitution of the selenone group by the nitrogen atom of the carbamate. Enantiomerically pure 1,3-oxazolidin-2-one derivatives can be easily prepared by using enantiomerically pure ,-hydroxyalkyl phenyl selenides as starting materials. [source] Preparation of Optically Active ,-Amino[3]ferrocenophanes , Building Blocks for Chelate Ligands in Asymmetric CatalysisEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 23 2003Patrick Liptau Treatment of 1,1,-diacetylferrocene (4) with dimethylamine and TiCl4 yielded the unsaturated dimethylamino-substituted [3]ferrocenophane product 5. Its catalytic hydrogenation gave the corresponding saturated [3]ferrocenophane system 6 (trans/cis , 7:1). The rac -[3]ferrocenophane amine 6 was partially resolved (to ca. 80% ee) by means of L - or D - O,O, -dibenzoyltartrate salt formation. Treatment of 4 with the pure (R)- or (S)-methyl(1-phenylethyl)amine (8)/TiCl4 gave the corresponding optically active unsaturated [3]ferrocenophane amines (R)-(+)- 9 and (S)-(,)- 9, respectively. Their catalytic hydrogenation again proceeded trans -selectively, giving the corresponding saturated diastereomeric [3]ferrocenophane amines (1R,3R,5R)- 10a and (1S,3S,5R)- 10b [starting from (R)- 9], their enantiomers ent - 10a and ent - 10b were obtained from (S)- 9, but with a poor asymmetric induction (10a/10b < 2:1). Quaternization of 6 (CH3I) followed by amine exchange using (R)- or (S)-methyl(1-phenylethyl)amine (8), respectively, proceeded with overall retention. Subsequent chromatographic separation gave the pure diastereoisomers (1R,3R,5R)- 10a and (1S,3S,5R)- 10b [from (R)- 8, ent - 10a and ent - 10b from (S)- 8] in > 60% yield. Subsequently, the benzylic (1-phenylethyl) auxiliary was removed from the nitrogen atom by catalytic hydrogenolysis to yield the enantiomerically pure (> 98%) ([3]ferrocenophanyl)methylamines (1R,3R)- 11 and (1S,3S)- 11, respectively, which were converted into the corresponding dimethylamino-substituted [3]ferrocenophanes (1R,3R)- 6 and (1S,3S)- 6. Each enantiomer from the following enantiomeric pairs was isolated in its pure form and characterized by X-ray diffraction: (R)- 9/(S)- 9; (1R,3R,5R)- 10a/(1S,3S,5S)- 10a; (1R,3R,5S)- 10b/(1S,3S,5R)- 10b; (1R,3R)- 11/(1S,3S)- 11. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] An Asymmetric Tandem Conjugative Addition-Intramolecular Cyclisation Process to Provide Functionalised 3,6-Dihydropyrans and 4,5-EpoxytetrahydropyransEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 1 2010Silvia Catalán-Muñoz Abstract The synthesis of 3,6-dihydropyrans and 4,5-epoxytetrahydropyrans starting from enantiomerically pure ,-hydroxy aldehyde (prepared by an organocatalytic aldol reaction) is described. The key step is a tandem sequence, which consists of a base-promoted conjugative addition to a vinyl onium salt, followed by either an intramolecular Wittig process to provide 3,6-dihydropyran derivatives or an intramolecular cyclisation/epoxidation process to afford 4,5-epoxytetrahydropyran scaffolds. The products obtained by this method are common substructures in polyketide natural products. [source] Asymmetric Synthesis of a Novel Conformationally Constrained D -Lysine Analogue with a Piperidine SkeletonEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 20 2008Pablo Etayo Abstract A practical asymmetric synthesis of enantiomerically pure(2R,4R)-1-(tert -butoxycarbonyl)-4-[2-(methoxycarbonylamino)ethyl]pipecolic acid starting from easily accessible (R)-2-[(S)-1,2-bis(benzyloxy)ethyl]-1-[(S)-1-phenylethyl]-4-piperidone in around 33,% overall yield has been performed. The efficiency of the synthetic strategy developed for the synthesis of this novel conformationally constrained D -lysine analogue relies on the high-yielding Wadsworth,Emmons reaction of a 2-substituted 4-piperidone and the diastereoselective reduction of the exocyclic C=C double bond at the 4-position of the piperidine ring.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Ring Expansion of 2-(,-Hydroxyalkyl)azetidines: A Synthetic Route to Functionalized PyrrolidinesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 19 2008François Durrat Abstract A series of 2-(,-hydroxyalkyl)azetidines synthesized from enantiomerically pure ,-amino alcohols and presenting various patterns both on the four-membered ring and on the adjacent hydroxy group were treated with either thionyl chloride or methanesulfonyl chloride in the presence of triethylamine. The thus-prepared 2-(,-chloro- or ,-methanesulfonyloxyalkyl)azetidines were shown to rearrange stereospecifically into 3-(chloro- or methanesulfonyloxy)pyrrolidines. When this rearrangement is conducted in the presence of an added nucleophile (NaN3, KCN, KOH, or NaOAc), the produced pyrrolidine incorporates the added nucleophile at C-3 stereospecifically. The relative configuration of the substituents in the formed pyrrolidines is consistent with a mechanism involving the formation of an intermediate bicyclic aziridinium ion, which is opened regioselectively at the bridgehead carbon atom. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Concise Synthesis of 2,6-Disubstituted Morpholines by Cyclization of Epoxy AlcoholsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 13 2007Domenico Albanese Abstract A novel, straightforward and high yielding synthesis of enantiomerically pure 2,6-disubstituted morpholines was developed by acid-catalyzed cyclization of epoxy alcohols. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Chiral 6,6,-Bis(oxazolyl)-1,1,-biphenyls as Ligands for Copper(I)-Catalyzed Asymmetric CyclopropanationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2007Karamali Khanbabaee Abstract A series of chiral bis(oxazoline)s with biphenyl backbones were synthesized from enantiomerically pure (S)- and (R)-hexabenzyloxydiphenic acid (1) and their utility in copper(I)-catalyzed asymmetric cyclopropanation was investigated. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Synthesis of Enantiomerically Pure 2,3,4,6-Tetrasubstituted Tetrahydropyrans by Prins-Type Cyclization of Methyl Ricinoleate and Aldehydes,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2006Ursula Biermann Abstract The AlCl3 -catalyzed Prins-type cyclization of methyl ricinoleate (1), an enantiomerically pure renewable compound, with aldehydes such as heptanal (2a), isobutyraldehyde (2b), pivaldehyde (2c) and benzaldehyde (2d) is a simple reaction for the diastereoselective synthesis of enantiomerically pure 2,3,6-trialkyl-substituted 4-chlorotetrahydropyrans. The respective 4-hydroxytetrahydropyrans are obtained e.g. with aldehydes 2a and 2d using montmorillonite KSF/O as the catalyst. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] A Lewis Acid Promoted Asymmetric Umpolung Reaction with ChiralN -Sulfinyl Imines as the ElectrophilesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 9 2005Xin Xu Abstract An new asymmetric umpolung reaction has been developed by reacting N -sulfinyl imines with 2-lithio-2-phenyl-1,3-dithiane. The reaction was conducted at between ,20 and,25 °C in THF in the presence of Et2AlCl as the Lewis acid promoter. Excellent diastereoselectivities (up to >95,% de) and chemical yields (64,95,%) have been achieved for nine substrates with all individual isomers separated and characterized. The absolute structure of the chiral products has been unambiguously determined by synthetic conversions to a known sample. 2-Lithio-2-phenyl-1,3-dithiane was found to be much less reactive than its 2-methyl counterpart, which was reported very recently. All individual isomers have been readily separated by column chromatography. The absolute structure of the chiral products has been unambiguously determined by conversion into a known compound. This method provides an easy access to enantiomerically pure ,-amino ketones. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] An Efficient Asymmetric Synthesis of 2-Substituted 1,4-Benzodiazepin-3-one as a Potential Molecular ScaffoldEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 8 2005Nuria Cabedo Abstract 2-Substituted 1,4-benzodiazepine-2-one compounds (9,12) were obtained by a highly diastereoselective alkylation of a seven-membered ring benzolactam (8) in the presence of (R)-phenylglycinol as a chiral inductor. The corresponding acid derivative (16) afforded a conformationally constrained structure suitable for preparing peptidomimetic analogues useful as a novel molecular scaffold. After cleavage of the chiral appendage this approach might also lead efficiently to enantiomerically pure 2-substituted benzodiazepines (15). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] New Monodentate P,C-Stereogenic Bicyclic Phosphanes: 1-Phenyl-1,3a,4,5,6,6a-hexahydrocyclopenta[b]phosphole and 1-Phenyloctahydrocyclopenta[b]phospholeEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2004Zbigniew Pakulski Abstract Racemic1-phenyl-1,3a,4,5,6,6a-hexahydrocyclopenta[b]phosphole (4) was separated into enantiomerically pure 1-phenyl-1,3a,4,5,6,6a-hexahydrocyclopenta[b]phosphole 1-oxides [(RP)- 6 and (SP)- 6] by an oxidative resolution procedure involving treatment of 4 with menthyl bromoacetate, crystallization of the resulting diastereoisomeric phosphonium bromides 8, and stereoselective hydrolysis of the diastereomerically pure salts to the corresponding enantiomerically pure phosphane oxides. Stereoretentive reduction of P=O in (RP)- 6 gave enantiomerically pure (SP)- 4. Hydrogenation of (SP)- 6 and subsequent reduction of P=O afforded saturated 1-phenyloctahydrocyclopenta[b]phosphole [(RP)- 5]. Monophosphanes (SP)- 4 and (RP)- 5 were tested as chiral ligands and catalysts in model asymmetric hydrogenation and C,C bond-forming reactions. Enantioselectivities of up to 95% were observed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Highly Enantioselective Synthesis of No-Carrier-Added 6-[18F]Fluoro- L -dopa by Chiral Phase-Transfer AlkylationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 13 2004Christian Lemaire Abstract [18F]Fluoro- L -dopa, an important radiopharmaceutical for positron emission tomography (PET), has been synthesized using a phase-transfer alkylation reaction. A chiral quaternary ammonium salt derived from a Cinchona alkaloid served as phase-transfer catalyst for the enantioselective alkylation of a glycine derivative. The active methylene group of this Schiff-base substrate was deprotonated with cesium hydroxide and rapidly alkylated by the 2-[18F]fluoro-4,5-dimethoxybenzyl halide (X = Br, I). The reaction proceeded with high yield (> 90%) at 0 °C or room temperature in various solvents such as toluene or dichloromethane. Preparation of the [18F]alkylating agent on a solid support was developed. After labelling, the labeled [18F]fluoroveratraldehyde was trapped on a tC18 cartridge and then converted on the cartridge into the corresponding benzyl halide derivatives by addition of aqueous sodium borohydride and gaseous hydrobromic or -iodic acid. Hydrolysis and purification by preparative HPLC made 6-[18F]fluoro- L -dopa ready for human injection in a 25,30% decay-corrected radiochemical yield in a synthesis time of 100 min. The product was found to be chemically, radiochemically and enantiomerically pure (ee > 95%). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Synthesis of Enantiomerically Pure 1,5,5-Trideuterated cis- and trans -2,4-Dioxa-3-phosphadecalins. 31P-NMR Evidence of Covalent-Bond Formation and the Stereochemical Implications in the Course of the Inhibition of , -ChymotrypsinHELVETICA CHIMICA ACTA, Issue 11 2007Markus Abstract The irreversible inhibition of , -chymotrypsin with the enantiomerically pure, P(3)-axially and P(3)-equatorially X-substituted cis- and trans- configurated 2,4-dioxa-3-phospha(1,5,5- 2H3)bicyclo[4.4.0]decane 3-oxides (X=F, 2,4-dinitrophenoxy) was monitored by 31P-NMR spectroscopy. 1H-Correlated 31P{2H}-NMR spectra enabled the direct observation of the vicinal coupling (3J) between the P-atom of the inhibitor and the CH2O moiety of Ser195 (=,Ser195'(CH2O)), thus establishing the covalent nature of the ,Ser195'(CH2OP) bond in the inhibited enzyme. The stereochemical course of the phosphorylation is dependent on the structure of the inhibitor, and neat inversion, both inversion and retention, as well as neat retention of the configuration at the P-atom was found. [source] The Nonchiral Bislactim Diethoxy Ether as a Highly Stereo-Inducing Synthon for Sterically Hindered, , -Branched , -Amino Acids: A Practical, Large-Scale Route to an Intermediate of the Novel Renin Inhibitor AliskirenHELVETICA CHIMICA ACTA, Issue 8 2003Richard Göschke The diastereoselective synthesis of the sterically hindered, , -branched , -amino acid derivative (2S,4S)- 24a and its N -[(tert -butoxy)carbonyl](Boc)-protected alcohol (2S,4S)- 19, both key intermediates of a novel class of nonpeptide renin inhibitors such as aliskiren (1), is described. Initially, the analogous methyl ester (2S,4S)- 17 was obtained by alkylation of the chiral Schöllkopf dihydropyrazine (R)- 12a with the dialkoxy-substituted alkyl bromide (R)- 11a, which proceeded with explicitly high diastereofacial selectivity (ds ,98%) to give (2S,5R,2,S)- 13a (Scheme,4), followed by mild acid hydrolysis and N -Boc protection (Scheme,5). Conversely, the complete lack of stereocontrol and poor yields for the reaction of (R)- 11a with the enantiomeric (S)- 12b suggested, in addition to the anticipated shielding effect by the iPr group at C(2) of the auxiliary, steric repulsion between the MeOC(6) and the bulky residues of (R)- 11a in the proposed transition state, which would strongly disfavor both the Si and Re attack of the electrophile (see Fig.). Based on this rationale, alkylation of the readily accessible achiral diethoxy-dihydropyrazine 21 with (R)- 11a was found to provide a 95,:,5 mixture of diastereoisomers (2S,2,S)- 22a and (2R,2,S)- 23a in high yield (Scheme,6), which afforded in two steps and after recrystallization enantiomerically pure (2S,4S)- 24a. Similarly, the stereochemical course for the alkylation reactions of the related alkyl bromides (S)- 28a and (R)- 28b with both (R)- 12a and (S)- 12b as well as with the achiral 21 was investigated (Schemes,7,9). The precursor bromides (R)- 11a, (S)- 11b, (R)- 28a, and (S)- 28b were efficiently synthesized via the diastereoselective alkylation of the Evans 3-isovaleroyloxazolidin-2-ones (R)- 7a and (S)- 7b either with bromide 6 or with benzyl chloromethyl ether, and subsequent standard transformations (Schemes,3 and 7). A practical and economical protocol of the preparation of (2S,4S)- 24a on a multi-100-g scale is given. This is the first report of the application of an achiral dihydropyrazine, i.e., in form of 21, as a highly stereo-inducing synthon providing rapid access to a N -protected , -branched , -amino acid with (2S) absolute configuration. [source] | ||||||||||||||||||||||||||||