Diastereoselective Synthesis of β-Substituted α-Methylserines via Chelated Alanine Ester Enolates

Grandel, Roland; Kazmaier, Uli

doi:10.1002/(sici)1099-0690(199802)1998:2<409::aid-ejoc409>3.0.co;2-2

Cited by 29 publications

(18 citation statements)

References 43 publications

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“…mL) was added dropwise. The reaction was quenched after 1 h with saturated aqueous NH 4 6,128.3,128.6,128.7,131.8,141.0,163.8,170.4. Ϫ C 17 H 15 NO 3 Hydroxy Amido Esters 8: A solution of oxazolines 6 and 7 (0.5 (281.3): calcd.…”

Section: Methodsmentioning

confidence: 99%

“…[1] (Equation 1). While various syntheses of α-alkylated α-am-In particular, some biologically active structures contain αino acids have been described in the literature, [6] few methhydroxy β-amino acids. For instance, (2R,3S)-phenylisoserods for the preparation of syn-α-alkyl α-hydroxy β-amino ine is an important component of taxol (paclitaxel), which acids have been reported.…”

Section: Introductionmentioning

confidence: 99%

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A New Diastereoselective Synthesis of anti-α-Alkyl α-Hydroxy β-Amino Acids

Cardillo¹,

Tolomelli

Tomasini³

1999

Eur. J. Org. Chem.

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Keywords: Alkylation / Oxazolines / anti-α-Alkyl α-hydroxy β-amino acids / Lithium dianion / Penicillin G acylase As part of an ongoing project concerning the synthesis of conditions, affording in quantitative yield the corresponding hydroxy amides. The starting (R)-3-amino-3-phenylenantiomerically pure α-hydroxy β-amino acids, we have now developed a general strategy allowing the synthesis of propanoic acid and (S)-3-aminobutanoic acid were obtained in enantiomerically pure form by selective enzymatic anti-α-alkyl α-hydroxy β-amino acids. Our procedure involves the intermediate formation of trans-oxazolines, hydrolysis of the corresponding phenylacetylamides with penicillin G acylase. which are alkylated at C-5 with good to high diastereoselectivity and then hydrolysed under mildly acidic have now developed a general strategy allowing the intro-

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A New Diastereoselective Synthesis of anti-α-Alkyl α-Hydroxy β-Amino Acids

Cardillo¹,

Tolomelli

Tomasini³

1999

Eur. J. Org. Chem.

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“…The relative configuration of the oxetanes (6) was confirmed by NMR spectroscopy and spectral comparison with representative literatureknown products (anti-7) (34)(35)(36)(37).…”

Section: Resultsmentioning

confidence: 99%

Photo aldol reactions with 5-methoxyoxazoles: Highly regio- and diastereoselective synthesis of α-amino β-hydroxy carboxylic acid derivatives

Griesbeck¹,

Bondock²

2003

Can. J. Chem.

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A versatile route to derivatives of α-amino β-hydroxy carboxylic acids, either with tertiary (from a corresponding glycine equivalent) or a quaternary α-carbon center is described. The key reaction is the cycloaddition of electronically excited carbonyl compounds (aromatic and aliphatic aldehydes, respectively) to oxazoles. To make the products hydrolytically more labile, a methoxy substituent at position C-5 was introduced leading to the formation of cycloadducts with an orthoester substructure. The photocycloaddition, either with triplet excited (aromatic) carbonyls or with singlet excited (aliphatic) carbonyls, led to the formation of mixtures of endo-and exo-diastereoisomers with moderate to very high exo-selectivities. The 4-unsubstituted 5-methoxyoxazole 1 (glycine equivalent) gave the [2 + 2]-adducts 3a-3f with aldehydes 2a-2f in high yields and excellent diastereoselectivities. Hydrolysis of these compounds resulted in the α-amino β-hydroxy esters 4a-4f with preferred erythro (S*,S*) configuration. As an extension of this process, 4-alkylated 5-methoxyoxazoles 5a-5f were applied as alkene components and the corresponding cycloadducts with benzaldehyde 6a-6f were obtained. Again, the exo-diastereoisomers were formed as the major products in diastereoselectivities from 73:27 (exo:endo) up to >95:5. Hydrolysis of these adducts resulted in the formation of α-amino β-hydroxy esters 7a-7f with like (S*,S*) configuration of the major diastereoisomers.Résumé : On décrit une voie versatile pour obtenir des acides α-amino-β-hydroxycarboxyliques portant des centres α-carbonés tertiaire (à partir de la glycine équivalente correspondante) ou quaternaire. La réaction clé est une cycloaddition de composés carbonylés électroniquement excités (aldéhydes aromatiques et aliphatiques respectivement) à des oxazoles. Afin de que les produits soient plus facilement hydrolysables, on a introduit un substituant méthoxyle en position C-5 afin d'obtenir des cycloadduits comportant une structure orthoester. La photocycloaddition, avec des carbonyles (aromatiques) excités à l'état triplet ou avec des carbonyles (aliphatiques) excités à l'état singulet, conduit à la formation de mélanges de diastéréomères endo-et exo-dans lesquels la sélectivité en faveur de l'exo-est de modérée à très élevée. La réaction du 5-méthoxyoxazole non substitué en position 4 (1) (équivalent de la glycine) avec les aldéhy-des 2a-2f donne les adduits [2 + 2] 3a-3f avec des rendements élevés et d'excellentes diastéréosélectivités. L'hydrolyse de ces composés conduit aux α-amino-β-hydroxyesters 4a-4f avec la configuration érythro (S*,S*) pré-férée. Comme extension de ce procédé, on a utilisé les 5-méthoxyoxazoles alkylées en position 4 (5a-5f) comme composants alcéniques et, par réaction avec les benzaldéhyde, on a obtenu les cycloadduits correspondants 6a-6f. Une fois de plus, les diastéréoisomères se forment comme produits majeurs, avec des diastéréosélectivités allant de 73:27 (exo:endo) jusqu'à >95:5. L'hydrolyse de ces produits conduit à la formation des α...

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“…determination) (Fesko et al 2010). The elution order of the different stereoisoimers was elucidated by analyzing reference compounds, e.g., commercially available DL-threo-β-phenylserine (Sigma-Aldrich), chemically synthesized DL-anti-phenylserine (Steinreiber et al 2007a) and DL-anti-methylthreonine (Dietz and Gröger 2009 (Grandel and Kazmaier 1998;Avenoza et al 2004). …”

Section: Generalmentioning

confidence: 99%

Expanding the threonine aldolase toolbox for the asymmetric synthesis of tertiary α-amino acids

Fesko

Strohmeier

Breinbauer

2015

Appl Microbiol Biotechnol

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The direct biochemical synthesis of tertiary α-amino acids with a wide range of diversity was recently reported using natural threonine aldolases LTA from Aeromonas jandei and DTA from Pseudomonas sp. Here, we describe the identification of five novel threonine aldolases which accept alanine and serine as amino acid donors. The enzymes were found by sequence database analysis using known aldolases as template. All enzymes were overexpressed in Escherichia coli and purified, and their biochemical properties were characterized. The new enantiocomplementary L- and D-threonine aldolases catalyze the asymmetric synthesis of β-hydroxy α-methyl- and α-hydroxymethyl-α-amino acids with good conversion and perfect enantioselectivity at α-carbon of the products (e.e. >99 %). The structural basis for the broad donor specificity of these threonine aldolases is analyzed based on crystal structure alignments and amino acid sequences comparison.

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Diastereoselective Synthesis of β-Substituted α-Methylserines via Chelated Alanine Ester Enolates

Cited by 29 publications

References 43 publications

A New Diastereoselective Synthesis of anti-α-Alkyl α-Hydroxy β-Amino Acids

A New Diastereoselective Synthesis of anti-α-Alkyl α-Hydroxy β-Amino Acids

Photo aldol reactions with 5-methoxyoxazoles: Highly regio- and diastereoselective synthesis of α-amino β-hydroxy carboxylic acid derivatives

Expanding the threonine aldolase toolbox for the asymmetric synthesis of tertiary α-amino acids

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