Synthesis of Enantiomerically Pure β- and γ-Amino Acids from Aspartic and Glutamic Acid Derivatives

Marini, Amedeo; Roumestant, M. L.; Viallefont, Ph.; Razafindramboa, D.; Bonato, M.; Follet, M.

doi:10.1055/s-1992-26315

Cited by 39 publications

(25 citation statements)

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“…There are two general routes for the synthesis of γ -amino acids: modification of glutamic acid and homologation of α-amino acids. The multistep derivatization of the α-carboxy function of glutamic acid using alkyl cuprates [16] has a major limitation, i.e. the incompatibility of cuprates with many functionalities, while the use of βamido zinc derivatives obtained from glutamic acid has been demonstrated only for the synthesis of homophenylalanine derivatives [17].…”

Section: Introductionmentioning

confidence: 99%

Efficient protocols for the synthesis of enantiopure γ‐amino acids with proteinogenic side chains

Loukas

Noula

Kokotos

2003

Journal of Peptide Science

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The synthesis of enantiopure gamma-substituted gamma-amino acids with proteinogenic side chains, starting from the corresponding natural alpha-amino acids, was studied. N-Protected amino aldehydes containing various protective groups were prepared from the corresponding amino alcohols by oxidation with NaOCl in the presence of AcNH-TEMPO and directly reacted with methyl, benzyl and tert-butyl phosphoranylidene acetate to produce alpha,beta-unsaturated gamma-amino esters. Simultaneous hydrogenation of the double bond and removal of either the benzyl or benzyloxycarbonyl group led to N- or C-protected gamma-amino acids in high yield. The enantiomeric purity was studied by 1H NMR analysis of Mosher amides and chiral HPLC analysis.

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Section: Introductionmentioning

confidence: 99%

Efficient protocols for the synthesis of enantiopure γ‐amino acids with proteinogenic side chains

Loukas

Noula

Kokotos

2003

Journal of Peptide Science

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“…Reetz et al have shown a route to prepare a-hydroxy-g-amino acids starting from L-amino acids, by stereoselective [2,3]-Wittig rearrangement [22]. The use of tetramethylethylenediamine in the formation of the lithium enolate led to the preferential formation of one of the four possible diastereoisomers (43), as shown in Scheme 13.12. Compound (44) displays intramolecular hydrogen bonds arising from the amide group and the alcohol function as a conformational feature of the g-turn mimetic.…”

Section: G-amino Acidsmentioning

confidence: 99%

“…g-Amino acids have also been prepared by modification of glutamic acid [43] and by homologation of a-amino acids. Use of a zinc reagent in straight asymmetric synthesis of aryl g-amino acids (98) is described by Jackson et al (Scheme 13.29) [44].…”

Section: Miscellaneous Approachesmentioning

confidence: 99%

Synthesis of γ‐ and δ‐Amino Acids

Trabocchi

Menchi

Guarna

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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An area of significant importance that provides new dimensions to the field of molecular diversity and drug discovery is the area of peptidomimetics [1]. Biomedical research has reoriented towards the development of new drugs based on peptides and proteins, by introducing both structural and functional specific modifications, and maintaining the features responsible for biological activity. As a part of this research area, unnatural amino acids are of valuable interest in drug discovery and their use as new building blocks for the development of peptidomimetics with a high structural diversity level is of key interest. In particular, medicinal chemistry has taken advantage of the use of amino acid homologs to introduce elements of diversity for the generation of new molecules as drug candidates in the so-called peptidomimetic approach, where a peptide lead is processed into a new nonpeptidic molecule. The additional methylenic unit between the N-and C-termini in b-amino acids results in an increase of the molecular diversity in terms of the higher number of stereoisomers and functional group variety, and many synthetic approaches to the creation of b-amino acids have been published. There is great interest in these as a tool for medicinal chemistry [2] and in the field of b-peptides generally [3]. The g-and d-amino acids have garnered similar interest. In particular, the folding properties of g-[4] and d-peptides [5] have been investigated, as they have been proved to generate stable secondary structures. The homologation of a-amino acids into g-and d-units allows an enormous increase of the chemical diversity within the three and four atoms between the amino and carboxyl groups. Thus, additional substituents and stereocenters expand the number of compounds belonging to the class of g-and d-amino acids. g-Amino acids have been reported both in linear form, and with the amino and carboxyl groups separated or incorporated in a cyclic structure. In the case of d-amino acids, five-and six-membered rings have been mainly reported having two substituents variously tethered between the amino and carboxyl groups. Moreover, bicyclic and spiro compounds have been reported as constrained d-amino acids, especially in the field of peptidomimetics. The synthetic approaches for the preparation of

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“…134 Wei and Knaus 135 reported the synthesis of (S)-vigabatrin 2 using (R)-methionine as the starting material via a onepot reduction-homologation. In this context, esterification of (R)-methionine with thionyl chloride in methanol followed by treatment with benzyl chloroformate gave (R)- Roumestant et al 136 have reported an efficient synthesis of enantiomerically pure N-Boc-c-amino acid 299c using glutamic acid as the starting material. In this context, the reaction of N-Boc-glutamic acid monomethyl ester 332 obtained from commercially available methyl glutamate hydrochloride, with ClCO 2 sec-Bu followed by reduction with NaBH 4 afforded alcohol derivative 333 in 82% yield.…”

Section: C-substituted C-amino Acidsmentioning

confidence: 99%