The asymmetric synthesis of γ-substituted glutamic acid derivatives via a glutamic acid γ-enolate synthon

Bosco, Marcella; Johnstone, Andrew N.C.; Bazza, Giorgia; Lopatriello, S.; North, Michael

doi:10.1016/0040-4020(95)00455-h

Cited by 15 publications

(3 citation statements)

References 79 publications

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“…These pathways illustrate a general strategy for obtaining a wide variety of N,O-protected pyroglutaminols. This class of compounds was selected as substrates in preference to protected pyroglutamates and acyclic glutamates based on some unpromising preliminary results involving N-Boc pyroglutamate ethyl ester and concerns over unwanted side reactions such as α-carbon racemization which are possible in the presence of an excess of various strong bases . Path A allows access to trityl or silyl ether protection at the primary alcohol (R) with any desired amide protecting group (R‘).…”

Section: Resultsmentioning

confidence: 99%

Electrophilic Fluorination of Pyroglutamic Acid Derivatives: Application of Substrate-Dependent Reactivity and Diastereoselectivity to the Synthesis of Optically Active 4-Fluoroglutamic Acids

Konas

Coward

2001

J. Org. Chem.

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Electrophilic fluorination of enantiomerically pure 2-pyrrolidinones (4) derived from (L)-glutamic acid has been investigated as a method for the synthesis of single stereoisomers of 4-fluorinated glutamic acids. Reaction of the lactam enolate derived from 9 with NFSi results in a completely diastereoselective monofluorination reaction to yield the monocyclic trans-substituted alpha-fluoro lactam product 21. Unfortunately, a decreased kinetic acidity in 21 and other structurally related monofluorinated products renders them resistant to a second fluorination. In contrast, the bicyclic lactam 12 is readily difluorinated under the standard conditions described to yield the alpha,alpha-difluoro lactam 24. The difference in reactivity between the two types of related lactams is attributed mainly to the presence or lack of a steric interaction between the base used for deprotonation and the protecting group present in the pyrrolidinone substrates. This conclusion was reached based on analysis of the X-ray crystal structure of 21, molecular modeling, and experimental evidence. The key intermediates 21 and 24 are converted to (2S,4R)-4-fluoroglutamic acid and (2S)-4,4-difluoroglutamic acid, respectively.

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Section: Resultsmentioning

confidence: 99%

Electrophilic Fluorination of Pyroglutamic Acid Derivatives: Application of Substrate-Dependent Reactivity and Diastereoselectivity to the Synthesis of Optically Active 4-Fluoroglutamic Acids

Konas

Coward

2001

J. Org. Chem.

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“…Under these conditions the aldehyde immediately reacted with the Z-protected amino group to give the methoxyaminal, which was further reduced to enantiomerically pure trans-2,4-piperidine dicarboxylate. 73 The corresponding cis-2,4-piperidine dicarboxylates were obtained very similarly by Hanessian. 74 Meyer reported a related concept for the synthesis of (-)-cassine.…”

Section: Scheme 32mentioning

confidence: 93%

Stereoselective Synthesis of Piperidines

Laschat¹,

Dickner²

2000

Synthesis

383

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“…In spite of its biological relevance, only a few methods have been reported for the preparation of racemic trans- or cis -piperidine-2,4-dicarboxylic acid . In addition, two asymmetric syntheses of enantiopure piperidine-2,4-dicarboxylic acid derivatives of 2 S configuration have been described …”

mentioning

confidence: 99%

Asymmetric Homologation of Ketones. A New Entry to Orthogonally Protected (2R,4R)-Piperidine-2,4-dicarboxylic Acid

et al. 2008

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A new conformationally constrained analogue of glutamic acid has been synthesized efficiently in seven steps from a chiral 2-alkyl-4-piperidone. The synthesis is based on (a) the unprecedented asymmetric one-carbon homologation of the ketone controlled by the size of the N-substituent and (b) the appropriate manipulation of substituents at positions 2 and 4 of the piperidine ring, a step that involves two independent oxidation processes.

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The asymmetric synthesis of γ-substituted glutamic acid derivatives via a glutamic acid γ-enolate synthon

Cited by 15 publications

References 79 publications

Electrophilic Fluorination of Pyroglutamic Acid Derivatives: Application of Substrate-Dependent Reactivity and Diastereoselectivity to the Synthesis of Optically Active 4-Fluoroglutamic Acids

Electrophilic Fluorination of Pyroglutamic Acid Derivatives: Application of Substrate-Dependent Reactivity and Diastereoselectivity to the Synthesis of Optically Active 4-Fluoroglutamic Acids

Stereoselective Synthesis of Piperidines

Asymmetric Homologation of Ketones. A New Entry to Orthogonally Protected (2R,4R)-Piperidine-2,4-dicarboxylic Acid

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