An Efficient Synthesis of Optically Pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-ama) and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-aml)

An efficient synthesis of enantiomerically pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-Ama) 1a and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L -phenylalanine cyclohexylamide ( 2 ) as chiral auxiliary. The free amino acids 1a, b were converted to the N^α-Boc,N^γ-Z-protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b , and 9b , the absolute configurations in both series were determined. β-Turn type-I geometries were observed for structures 8b and 9b , whereas 8a crystallized in an extended backbone conformation.     

由(S)-和( R )-天冬氨酸合成( R )-和(S)-(2-苄氧乙基)环氧乙烷的改良方法

苄氧乙基环氧乙烷;不对称合成;由(S)-和( R )-天冬氨酸合成( R )-和(S)-(2-苄氧乙基)环氧乙烷的改良方法     

Asymmetric total synthesis of 14(R),15(S)-, 14(S),15(R)-, 14(R),15(R)-, and 14(S),15(S)-epoxyeicosatrienoic acids

The four chiral stereoisomers of 14,15-oxido-5Z, 8Z, 11Z-eicosatrienoic acid were synthesized. The absolute stereochemistry in each case was derived from an asymmetric epoxidation of E-2-octen-1-ol.     

Determination of (S)-(-)-cathinone and its metabolites (R,S)-(-)-norephedrine and (R,R)-(-)-norpseudoephedrine in urine by high-performance liquid chromatography with photodiode-array detection.

A high-performance liquid chromatographic (HPLC) procedure with photodiode-array detection (DAD) is described for the determination of (S)-(-)-cathinone (S-CA) and its metabolites (R,S)-(-)-norephedrine (R-NE) and (R,R)-(-)-norpseudoephedrine (R-NPE) in urine. Extraction and clean-up of 1-ml urine samples were performed on a cyano-bonded solid-phase column using (+/-)-amphetamine as internal standard. The concentrated extracts were separated on a 3-microns ODS-1 column with acetonitrile-water-phosphoric acid-hexylamine as the mobile phase. Peak detection was done at 192 nm. The detection limits for S-CA and R-NE/R-NPE in urine were 50 and 25 ng/ml, respectively. The differentiation of the enantiomers of cathinone and norephedrine was achieved by derivatization with (S)-(-)-1-phenylethyl isocyanate to the corresponding diastereomers followed by HPLC-DAD on a 5-microns normal-phase column. The R and S enantiomers of norpseudoephedrine were determined by gas chromatography-mass spectrometry after on-column derivatization with (S)-(-)-N-trifluoroacetylprolyl chloride. Following a single oral dose of 0.5 mg/kg of S-CA, the concentrations found in urine ranged from 0.2 to 3.8 micrograms/ml of S-CA, from 7.2 to 46.0 micrograms/ml of R-NE and from 0.5 to 2.5 micrograms/ml of R-NPE.     

Synthesis of enantiopure (R,R)- and (S,S)-cis-2,3-propanoprolines

A novel approach to the synthesis of an enantiopure bicyclic proline analogue, hexahydrocyclopenta[b]pyrrole-6a(1H)-carboxylic acid (‘2,3-propanoproline’), has been developed. The method relied on tandem Strecker-nucleophilic cyclization reaction of 2-(2-bromoethyl)cyclopentanone. The overall synthetic scheme included six steps and resulted in 18% overall yield of both enantiomers of the title amino acid.     

Synthesis of (5R,8S,10R)-6-(Allyloxy)- and (5R,8S,10R)-6-(Propyloxy)ergolines from the 6-Methyl Precursors

Novel (5R,8S,10R)-6-(allyloxy)- and (5R,8S,10R)-6-(propyloxy)ergolines have been synthesized by use of a Meisenheimer [2,3]-sigmatropic rearrangement of a (5R,8S,10R)-6-allyl-ergoline N⁶-oxide as key step.     

Total synthesis of (S)-(+)-curcudiol, and (S)-(+)- and (R)-(-)-curcuphenol.

A highly enantioselective synthesis of the versatile chiral synthons possessing one stereogenic center, (S)- and (R)-4-aryl-5-hydroxy-(2E)-pentenoate (3) was achieved based on the enzymatic reaction of (+/-)-3 with commercially available lipases MY-30 or OF-360 from Candida rugosa. Application of (S)-3 and (R)-3 to the total syntheses of(S)-curcuphenol (1), (S)-curcudiol (2), and (R)-curcuphenol (1), respectively, is described.     

Enantioselective syntheses of (S)- and (R)-8,9-dihydroxydihydromagnolol

8,9-Dihydroxydihydromagnolol 5 was synthesized in four steps in which the synthesis of magnolol 4 was improved and the absolute configuration of 5 was confirmed as (R).     

Asymmetric synthesis of (S,R)- and (R,R)-methiin stereoisomers

Abstract

An asymmetric synthesis of (+)- and (–)-methiine (S-methyl-(R)-cysteine sulfoxide) diastereomers has been developed. These natural sulfur compounds were isolated from a variety of Brassica vegetables. As the starting compound, (R)-cysteine was used, which was methylated to form (R)-S-methylcysteine. Then the oxidation of S-methylcysteine with tert-butyl hydroperoxide catalyzed by the chiral tetra(isopropylate)titanium/(S)- or (R)-Binol complex led to the formation of (1?R,2S)-(+)- or (1?R,2R)-(–)-methiin stereomers.     

Synthesis of (R)- and (S)-Oxymethylmorpholine Derivatives

(S)-N-benzyl-3-tert-butyldiphenylsilyloxymethylmorpholine and (R)-N-benzyl-3-benzyloxymethylmorpholine are synthesized starting from (R)-1-benzylglycerol.     

Stereoselective Formation of Ternary Copper(II) Complexes of (S)-Amino-acid Amides and (R)- or (S)-Histidine and (R)- or (S)-Tyrosine in Aqueous Solution

Formation constants of ternary complexes of Cu^II with (S)-amino-acid amides ((S)-phenylalaninamide, (S)-prolinamide, and (S)-tryptophanamide) and (R)- or (S)-histidine and (R)- or (S)-tyrosine were determined potentiometrically in aqueous solution. Significant stereoselectivity was presented by all three amides towards histidine, the diastereoisomeric complexes with ‘heterochiral’ ligands being more stable than those with ‘homochiral’ ligands (see Table 3). The stereoselectivity observed with (S)-phenylalaninamide and (S)-tryptophanamide may be explained on the basis of hydrophobic stacking interactions between 1H-imidazole and the aromatic side chain, favoured by the terdentate behaviour of histidine (see Fig.2), whereas repulsive effects seem to be prevalent with (S)-prolinamide. Only (S)-prolinamide and (S)-phenylalaninamide show appreciable stereoselectivity with tyrosine, which is bidentate, probably on account of repulsive interactions. The present results on the stability of ternary complexes in solution allow to draw some conclusions on the mechanism of chiral discrimination performed by Cu^II complexes of (S)-amino-acid amides added to the mobile phase in HPLC (reversed phase).     

Studies towards the synthesis of (1R,2S)- and (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonates and (1S,2S)- and (1R,2S)-2,3-epoxy-1-hydroxypropylphosphonates

The trans-configured fosfomycin analogue, diethyl (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonate, was synthesised by the intramolecular Williamson reaction of diethyl (1S,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate. The cis-analogue was obtained as O-ethyl or O,O-diethyl (1R,2S)-1,2-epoxy-3-hydroxypropylphosphonates, when (1R,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate or its 3-O-trityl derivative were used as starting materials, respectively. The intramolecular Williamson cyclisations of diethyl (1S,2R)- and (1R,2S)-1-benzyloxy-3-hydroxy-2-mesyloxypropylphosphonates led to diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, respectively, with the concomitant formation of diethyl (E)-1-benzyloxy-3-hydroxyprop-1-en-1-phosphonate. From diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, enantiomerically pure diethyl (1S,2S)- and (1R,2S)-1,2-dihydroxypropylphosphonates were obtained by catalytic hydrogenation, while diethyl (1S,2S)- and (1R,2S)-3-acetamido-1,2-dihydroxypropylphosphonates were produced after epoxide ring opening with dibenzylamine, acetylation and hydrogenolysis.     

Simultaneous determination of (R)- and (S)-naproxen and (R)- and (S)-6-O-desmethylnaproxen by high-performance liquid chromatography on a Chiral-AGP column.

A high-performance liquid chromatographic method for the simultaneous determination of both enantiomers of naproxen and its metabolite 6-O-desmethylnaproxen has been developed. The separation is performed on a column containing alpha 1-acid glycoprotein as the chiral selector. The method has been used for the determination of the enantiomeric purity of the drug substance and the metabolite, and for the simultaneous determination of all four compounds in biological fluids.     

(+)-(1S,2S,5R)-8-联苯薄荷醇的合成

以(R)-( )-pu legone为起始原料,经1,4-加成,还原两步反应合成了手性辅助试剂( )-(1S,2S,5R)-8-联苯薄荷醇及其差向异构体(-)-(1R,2S,5R)-8-联苯薄荷醇,总产率95%。其结构经1H NMR,13C NMR,IR,MS和X-射线衍射仪表征。     

The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid

Monohydroxylated polyunsaturated fatty acids belonging to the oxylipin class of natural products are present in marine and terrestrial sources as well as in the human body. Due to their biological activities and role in diverse biosynthetic pathways, oxylipins biosynthesized from eicosapentaenoic acid and arachidonic acid have attracted great interest from the scientific community. One example is 3-hydroxyeicosapentaenoic acid where the absolute configuration at C-3 has only been tentatively assigned. In this paper, studies on acetate type aldol reactions that enabled the preparation of 3-(R)-hydroxyeicosapentaenoic acid (3R-HETE, 2) and its enantiomer are presented.     

An enantioselective synthesis of (S)- and (R)-curcuphenol

The enantioselective synthesis of the phenolic sesquiterenses (S)- and (R)-curcuphenol is reported. The key step in this synthesis is the asymmetric conjugate addition using a readily available enantiomerically pure sulfoxide as the chiral auxiliary.