New methodologies for the asymmetric synthesis of peptides β3-cterminal aldehydes and disubstituted amino acid derivatives via heterocycloaddition
type: Dataset
contact point: Organization
  fn: CCSD
keyword: nitrone
keyword: couplage-peptidique-encombre
keyword: peptide-synthesis
keyword: chimothechemical-sciencesother
keyword: infoeu-reposemanticsdoctoralthesis
keyword: 13-dipolar-cycloaddition
keyword: oxazinone
keyword: synthese-peptidique
keyword: organocatalyseur
keyword: stereoselective
keyword: transacetalisation
keyword: organocatalyst
keyword: epimerisation
keyword: isoxazolidine
keyword: cycloaddition-dipolaire-13
keyword: hindered-peptide-coupling
keyword: -aminoaldehyde
keyword: 6-ato
keyword: theses
landing page: https://theses.hal.science/tel-00793512
description: Peptide aldehydes are known as protease inhibitors and precursors for many biologically active compounds. Methods for their synthesis involve classically the transformation of a precursor (Weinreb amide, ester, alcohol, acetal) into an aldehyde as one of the final steps to prevent epimerization of the carbon α to the aldehyde. By contrast, β-peptide aldehydes, more stable to epimerization, have been relatively unexplored. They are usually obtained by homologation of the corresponding amino acid despite low yielding steps, an epimerization problem and low number of accessible amino acids. Therefore, new synthetic access to β-peptide aldehydes is still a challenging problem. On the basis of previous work in our team concerning [4+2] and [3+2] diastereoselective cycloadditions, we have developed during this PhD thesis new strategies for the asymmetric access of β-amino acid derivatives by two complementary ways :1) Original six-membered heterocycles 6-ATO (6-alkoxy-tetrahydrooxazinone ) were prepared by a highly stereoselective heterocycloaddition reaction with good yields and de. These cycloadducts were transformed via transacetalisation into both «mixed» and «symmetrical» aminoacetals. Moreover, these new acetals are ideal intermediates for further peptide coupling, leading ultimately to monosubstituted β3-C-terminal peptide aldehydes. 2) By another approach five-membered heterocycles 5-AISO (3,3’-disubstituted 5-alkoxy-isoxazolidines) were obtained via 1,3-dipolar cycloaddition between α-keto ester nitrones and vinyl ether. These compounds were successfully used as precursors of disubstituted β-amino aldehydes after transprotection of the nitrogen atom and N-O cleavage of the isoxazolidine ring. Asymmetric extension of the cycloaddition step was studied by enantioselective and diastereoselective pathways, thus opening unprecedented entry to enantioenriched disubstituted β3,β3-C-terminal peptide aldehydes.
identifier: NNT: 2013LEMA1002
issued: 2026-05-14T05:32:00.738852
language: fr
modified: 2026-05-14T05:32:00.738860

test_moissonnage_selune
type: Agent

New methodologies for the asymmetric synthesis of peptides β3-cterminal aldehydes and disubstituted amino acid derivatives via heterocycloaddition
type: Distribution
access URL: https://theses.hal.science/tel-00793512
format: HTML
issued: 2026-05-14T05:32:00.791891
modified: 2026-05-14T05:32:00.675227