Concise Asymmetric Synthesis of β-Hydroxy α-Amino Acids Using the Sulfinimine-Mediated Asymmetric Strecker Synthesis:  Phenylserine and β-Hydroxyleucine

Chiral β‐hydroxy‐β‐arylalanine and β‐methoxy‐β‐arylalanine derivatives, which occur widely in marine nature products, were stereoselectively synthesized with 99 % ee values. The two erythro isomers were prepared by L‐ or D‐aminoacylase‐catalyzed resolution of the corresponding N‐acetyl derivatives, whereas the two threo isomers were obtained only by D‐aminoacylase‐catalyzed resolution of the derivatives. erythro‐β‐Hydroxy‐β‐arylalanine derivatives were prepared by diastereoselective hydrogenation of ethyl 2‐(hydroxyimino)‐3‐oxo‐3‐arylpropanoates, which were in turn acquired by the oximation of ethyl 3‐oxo‐3‐arylpropanoates with ethyl nitrite in the presence of nano‐K2CO3 with yields of 72 % to 80 %. β‐Methoxy‐β‐arylalanine derivatives were synthesized through Williamson reactions between the corresponding β‐hydroxy‐β‐arylalanines and iodomethane with silver oxide as base.

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“…[ α ] D 20 = 61.0 ( c = 0.4, 6 n HCl). [lit4b [ α ] D 20 = 60.7 ( c = 0.4, 6 n HCl).]. HPLC: column: Daicel Chem.…”

Section: Methodsmentioning

confidence: 99%

Biocatalytic Synthesis of Enantiopure β‐Methoxy‐β‐arylalanine Derivatives

et al. 2014

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“…[26] In this case, a preformed para-methoxyphenyl (PMP)-protected glyoxylate imine (37) reacts with an a-hydroxyketone (36) to afford the products with good diastereomeric ratios and excellent ee values (Scheme 13). Notably, the change in priority of the substituents around the C3 atom causes the stereochemistry to become 3S in the syn product (38). Extensive investigation with different organocatalysts rationalized the stereocontrol of the products.…”

Section: Mannich-type Reactionsmentioning

confidence: 99%

“…Extensive investigation with different organocatalysts rationalized the stereocontrol of the products. The use of (S)-proline (2-pyrrolidinecarboxylic acid) gave rise to an (E)-enamine (39) and overall syn selectivity in the Mannich product (38). [27] This selectivity was observed because the si face of the (E)-enamine reacted via transition state 40.…”

Section: Mannich-type Reactionsmentioning

confidence: 99%

“…Strecker Reaction Davis et al developed another route to b-hydroxy-a-amino acids by using a chiral-sulfinimine-mediated Strecker reaction (Scheme 18). [38] Treatment of a chiral aldehyde with chiral sulfonamide 57 in the presence of tetraethoxytitanium generated a chiral sulfinimine (58) in moderate yield. On treatment of the sulfinimine with ethylaluminium cyanoisopropoxide (generated in situ), a nitrile was added selectively onto the re face of the sulfinimine; the stereochemistry was controlled by the sulfinyl group.…”

Section: Sharpless Aminohydroxylation (Aa) and Sharpless Epoxidation mentioning

confidence: 99%

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Adding a Functional Handle to Nature′s Building Blocks: The Asymmetric Synthesis of β‐Hydroxy‐α‐Amino Acids

Zhang

Farrants

2014

Chemistry An Asian Journal

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β-Hydroxy-α-amino acids are not only used by synthetic chemists but are also found in natural products, many of which show anti-microbial or anti-cancer properties. Over the past 30 years, chemists have searched for many asymmetric routes to these useful building blocks. Initial attempts to synthesize these compounds utilized chiral auxiliaries and the reactions of glycine equivalents with aldehydes to form two stereocenters in one step. Other methods with the formation of specific intermediates or that were aimed at a specific amino acid have also been investigated. Asymmetric hydrogenation by dynamic kinetic resolution has emerged as a high-yielding method for the synthesis of an array of modified amino acids with good stereoselectivity. More recently, amino-acid functionalization and multicomponent reactions have increased the atom economy and simplified many long and difficult routes. In this Focus Review, many of the elegant syntheses of these compounds are explored. The applications of β-hydroxy-α-amino acids in natural-product synthesis are also mentioned.

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“…As substrate, the commercially available 2,4,5-trimethyloxazole was used and excellent (exo-)diastereoselectivities were observed for the photocycloaddition with aldehydes. An attractive family of target compounds, which might be available by this route, consists of derivatives of α-amino β-hydroxy carboxylic acids (21)(22)(23)(24)(25)(26), either with tertiary (from a corresponding glycine equivalent) or quaternary α-carbon centers (Fig. 1).…”

Section: Introductionmentioning

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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Concise Asymmetric Synthesis of β-Hydroxy α-Amino Acids Using the Sulfinimine-Mediated Asymmetric Strecker Synthesis: Phenylserine and β-Hydroxyleucine

Cited by 57 publications

References 45 publications

Biocatalytic Synthesis of Enantiopure β‐Methoxy‐β‐arylalanine Derivatives

Biocatalytic Synthesis of Enantiopure β‐Methoxy‐β‐arylalanine Derivatives

Adding a Functional Handle to Nature′s Building Blocks: The Asymmetric Synthesis of β‐Hydroxy‐α‐Amino Acids

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

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