Synthesis of β-Amino Acids Based on Oxidative Cleavage of Dihydropyridone Derivatives

Ege, Markus; Wanner, Klaus T.

doi:10.1021/ol0485518

Cited by 28 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 Construction of Site-Directed Mutants of PAM. TcPAM point mutants were generated using the QuikChange II sitedirected mutagenesis kit (Stratagene, La Jolla, CA) and Turbo Pfu polymerase (Stratagene, La Jolla, CA) along with the respective oligonucleotide primers: Y80F-For-(5 0 -AGACGGT GCTGATATCTTTGGCGTTACCACGGGTTTCGG-3 0 ) and L104A-For-(5 0 -GCAGGAGAGCGCCATCCGCTGTC-3 0 ).…”

mentioning

confidence: 99%

Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase

Feng

Wanninayake

Strom³

et al. 2011

Biochemistry

135

View full text Add to dashboard Cite

The structure of a phenylalanine aminomutase (TcPAM) from Taxus canadensis has been determined at 2.4 Å resolution. The active site of the TcPAM contains the signature 4-methylidene-1H-imidazol-5(4H)-one prosthesis, observed in all catalysts of the class I lyase-like family. This catalyst isomerizes (S)-α-phenylalanine to the (R)-β-isomer by exchange of the NH2/H pair. The stereochemistry of the TcPAM reaction product is opposite of the (S)-β-tyrosine made by the mechanistically related tyrosine aminomutase (SgTAM) from Streptomyces globisporus. Since TcPAM and SgTAM share similar tertiary- and quaternary-structures and have several highly conserved aliphatic residues positioned analogously in their active sites for substrate recognition, the divergent product stereochemistries of these catalysts likely cannot be explained by differences in active site architecture. The active site of the TcPAM structure also is in complex with (E)-cinnamate; the latter functions as both a substrate and an intermediate. To account for the distinct (3R)-β-amino acid stereochemistry catalyzed by TcPAM, the cinnamate skeleton must rotate the C1-Cα and Cipso-Cβ bonds 180° in the active site prior to exchange and rebinding of the NH2/H pair to the cinnamate, an event that is not required for the corresponding acrylate intermediate in the SgTAM reaction. Moreover, the aromatic ring of the intermediate makes only one direct hydrophobic interaction with Leu-104. A L104A mutant of TcPAM demonstrated an ∼1.5-fold increase in kcat and a decrease in KM values for sterically demanding 3'-methyl-α-phenylalanine and styryl-α-alanine substrates, compared to the kinetic parameters for TcPAM. These parameters did not change significantly for the mutant with 4'-methyl-α-phenylalanine compared to those for TcPAM.

show abstract

mentioning

confidence: 99%

Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase

Feng

Wanninayake

Strom³

et al. 2011

Biochemistry

135

View full text Add to dashboard Cite

show abstract

“…Many approaches to their synthesis have been developed [16][17][18][19][20][21]. Oxohydropyridines can also be used as precursors in the stereoselective synthesis of substituted [22] or disubstituted b-amino acids [23].…”

Section: Introductionmentioning

confidence: 99%

Unexpected transformation of ethyl 1-(4-chlorophenyl)-2-methyl-4-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate and antibacterial activity of the products

et al. 2014

View full text Add to dashboard Cite

The cyclization reaction of N-(4-chlorophenyl)-b-alanine, in the presence of piperidine as a catalyst, provided ethyl 1-(4-chlorophenyl)-2-methyl-4-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate, which reactions with different hydrazines were carried out resulting in formation of a variety of tetrahydropyridine, dihydropyrazolone, and oxazole derivatives in good yields. 5-[2-[(4-Chlorophenyl) amino]ethyl]-4-(1-hydrazinylethylidene)-2,4-dihydro-3H-pyrazol-3-one was converted into a series of hydrazones, which provided tetrahydro-3H-pyrazolo[4,3-c]pyridin-3-one under treatment with acids. The structures of all synthesized compounds were confirmed by IR, 1 H NMR, and 13 C NMR spectroscopy. The structures of three compounds were unambiguously assigned by means of X-ray analysis data. Some of the synthesized compounds exhibited weak antibacterial activity.

show abstract

“…In particular, the low solubility of salts such as 1 can lead to variable results and has hampered attempts to scale up the reduction.Recently, it has been demonstrated that similar unsubstituted dihydropyridones are accessible Via nucleophilic addition to 4-methoxy substituted pyridinium salts. [3][4][5][6] Encouraged by these results, we proposed that addition of Grignard reagents to pyridinium salts such as 1, followed by acidic…”

mentioning

confidence: 99%

“…Recently, it has been demonstrated that similar unsubstituted dihydropyridones are accessible via nucleophilic addition to 4-methoxy substituted pyridinium salts. − Encouraged by these results, we proposed that addition of Grignard reagents to pyridinium salts such as 1 , followed by acidic hydrolysis, could provide a useful alternative to the Birch reduction, but this time using the aromatic heterocycle as an electrophile.…”

mentioning

confidence: 99%

Regioselective Nucleophilic Addition to Pyridinium Salts: A New Route to Substituted Dihydropyridones

2009

View full text Add to dashboard Cite

The regioselective addition of nucleophiles to pyridinium salts generates an intermediate enol-ether, which can be hydrolyzed in situ to provide a range of dihydropyridones. Certain Grignards have shown inherent differences in the regioselectivity of addition to these salts, and this difference can be tuned to give single regioisomeric addition products. The dihydropyridone products can be further manipulated in many ways using standard transformations.

show abstract

Synthesis of β-Amino Acids Based on Oxidative Cleavage of Dihydropyridone Derivatives

Cited by 28 publications

References 23 publications

Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase

Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase

Unexpected transformation of ethyl 1-(4-chlorophenyl)-2-methyl-4-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate and antibacterial activity of the products

Regioselective Nucleophilic Addition to Pyridinium Salts: A New Route to Substituted Dihydropyridones

Contact Info

Product

Resources

About