- An efficient and stereodivergent synthesis of threo- and erythro-β-methylphenylalanine. Resolution of each racemic pair by semipreparative HPLC
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threo and erythro diastereoisomers of the constrained amino acid (βMe)Phe can be obtained separately on a multigram scale through a three-step synthesis from the corresponding Z and E isomers of 2-phenyl-4(α-phenylethylidene)-5(4H)-oxazolone. The 5(4H)-ox
- Alías, Miriam,López, María Pilar,Cativiela, Carlos
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p. 885 - 891
(2007/10/03)
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- A Versatile Chemo-Enzymatic Route to Enantiomerically Pure β-Branched α-Amino Acids
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A series of diastereoisomers of β-methyl-β-phenylalanine analogues 1a?f have been prepared in enantiomerically pure form using a combination of chemo- and biocatalysis. Starting from l-threonine methyl ester 2, a range of β,β-disubstituted didehydroamino
- Roff, Geoffrey J.,Lloyd, Richard C.,Turner, Nicholas J.
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p. 4098 - 4099
(2007/10/03)
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- Stereoinversion of β- and γ-substituted α-amino acids using a chemo-enzymatic oxidation-reduction procedure
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Both D- and L-β- and γ-substituted α-amino acids can be interconverted to their respective L- and D- diastereoisomers by treatment with an enantioselective amino acid oxidase and a chemical reducing agent.
- Enright, Alexis,Alexandre, Francois-Rene,Roff, Geoffrey,Fotheringham, Ian G.,Dawson, Michael J.,Turner, Nicholas J.
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p. 2636 - 2637
(2007/10/03)
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- A new strategy for the synthesis of four individual isomers of β-methylphenylalanine
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The application of an allylic strain effect in boron enolates and asymmetric Michael-like addition/electrophilic bromination reactions is reported for the asymmetric synthesis of the individual isomers of unusual constrained amino acids. For β-substituted
- Lung,Li,Lou,Hruby
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- Exploration for Large-scale Stereoselective Synthesis of Unusual Amino Acids by using 4-Phenyoxazolidin-2-one as a New Chiral Resolution Reagent
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Individual isomers of β-branched α-amino acids have been stereoselectively and asymmetrically synthesized in high yield by a new method which uses 4-phenyloxazolidin-2-one as a novel chiral resolution reagent acting simultaneously as the auxiliary.
- Li, Guigen,Patel, Dinesh,Hruby, Victor J.
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p. 3057 - 3060
(2007/10/02)
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- Development of a Model for the δ Opioid Receptor Pharmacophore. 2. Conformationally Restricted Phe3 Replacements in the Cyclic δ Receptor Selective Tetrapeptide Tyr-cOH (JOM-13)
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The in vitro pharmacological properties and conformational features of analogs of the δ opioid receptor selective tetrapeptide Tyr-cOH (JOM-13) in which the Phe3 residue was replaced by each of the four stereoisomers of β-methylphenylalanine (β-MePhe) were investigated.Both analogs in which the α carbon of the Phe3 replacement has L-stereochemistry display high affinity for δ receptors with the (2S,3S)-MePhe3 analog exhibiting approximately 8-fold higher affinity than the (2S,3R)-MePhe3 diastereomer.Surprisingly, one analog with D-stereochemistry in residue 3, the (2R,3R)-MePhe3 analog, also display high affinity for the δ receptor and is extraordinarily selective for this receptor.All analogs were agonists in the mouse vas deferens (MVD) and guinea pig ileum (GPI) smooth muscle bioassays, displaying MVD and GPI potencies consistent with their δ and μ opioid receptor affinities, respectively.The use of β-MePhe as a replacement for Phe3 was based upon the desire to reduce the conformational flexibility of the Phe3 side chain by imposing a steric rotational constraint in the form of the β-methyl substituent and to thus deduce the residue 3 side chain orientation in the δ receptor-bound conformation from the correlation between δ receptor binding affinities and conformational preferences.Molecular mechanics computations revealed, however, that the conformational constraints imposed by the β-methyl group in the (2S,3S)-MePhe3 and (2S,3R)-MePhe3 analogs were too modest to allow unequivocal determination of δ receptor-bound residue 3 side chain conformation.However, analysis of the high-affinity (2R,3R)-MePhe3 analog revealed a strong preference for a single side chain conformer (χ1 ca 60 deg).Low-energy conformers of this analog could only be effectively superimposed with low-energy conformers of the parent peptide in which the Phe3 side chain conformation was limited to χ1 ca -60 deg.This observation eliminates the last remaining uncertainty regarding conformational features of the pharmacophore elements in the δ receptor-bound state, allowing the proposal of a complete model.
- Mosberg, Henry I.,Omnaas, John R.,Lomize, Andrei,Heyl, Deborah L.,Nordan, Ian,et al.
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p. 4384 - 4391
(2007/10/02)
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- Asymmetric synthesis of unusual amino acids: An efficient synthesis of optically pure isomers of β-methylphenylalanine
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Substitution of the diastereotopic β-hydrogens of many α-amino acids provides an approach to the three dimensional topographic control of peptide structure. Asymmetric synthesis of the desired amino acids is needed to facilitate these studies. All four in
- Dharanipragada,VanHulle,Bannister,Bear,Kennedy,Hruby
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p. 4733 - 4748
(2007/10/02)
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- ASYMMETRIC SYNTHESIS OF UNUSUAL AMINO ACIDS: SYNTHESIS OF OPTICALLY PURE ISOMERS OF β-METHYLPHENYLALANINE
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All the four individual isomers of β-methylphenylalanine have been synthesized in very high optical purities by utilizing in part the chiral imide enolate bromination methodology of Evans and co-workers.
- Dharanipragada, Ramalinga,Nicolas, Ernesto,Toth, Geza,Hruby, Victor J.
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p. 6841 - 6844
(2007/10/02)
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