Synthesis of the first axially dissymmetric, C-alpha, alpha-disubstituted glycine containing a crown ether receptor, and the conformational preferences of a model peptide (Articolo in rivista)

Type
Label
  • Synthesis of the first axially dissymmetric, C-alpha, alpha-disubstituted glycine containing a crown ether receptor, and the conformational preferences of a model peptide (Articolo in rivista) (literal)
Anno
  • 2002-01-01T00:00:00+01:00 (literal)
Alternative label
  • Mazaleyrat J.P., Goubard Y., Azzini M.V., Wakselman M., Peggion C., Formaggio F., Toniolo C. (2002)
    Synthesis of the first axially dissymmetric, C-alpha, alpha-disubstituted glycine containing a crown ether receptor, and the conformational preferences of a model peptide
    in European journal of organic chemistry (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Mazaleyrat J.P., Goubard Y., Azzini M.V., Wakselman M., Peggion C., Formaggio F., Toniolo C. (literal)
Pagina inizio
  • 1232 (literal)
Pagina fine
  • 1247 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • Synthesis of the first axially dissymmetric, C-alpha, alpha-disubstituted glycine containing a crown ether receptor, and the conformational preferences of a model peptide (literal)
Abstract
  • Racemic and enantiomerically enriched N-alpha-protected methyl 6-amino-1,11-(20-crown-6)-6,7-dihydro-5H-dibenzo[a,c]-cycloheptene-6-carbox ylates (Boc-[20-C-6]-Bip-OMe) (RS)Ia, (R)-Ia and (S)-Ia have been synthesized by phase-transfer dialkylation of the 4-chlorobenzylidene derivative of glycine tert-butyl ester, with both racemic and resolved (both enantiomers) 2,2'-bis(bromomethyl)-6,6'-dimethoxy-1,1'-biphenyl being used as alkylating agents. Demethylation of the resulting (RS)-, (R)- and (S)-H-[MeO](2)-Bip-OtBu, followed by esterification and N-alpha-Boc protection, gave (RS)-, (R)- and (S)Boc-[HO](2)-Bip-OMe. Cyclization with Cs2CO3/DMF and pentaethylene glycol ditosylate afforded the crown-carrier C-alpha,C-alpha-disubstituted glycines (RS)-Ia, (R)-Ia and (S)-Ia, possessing only axial dissymmetry. Although (R)-Ia and (S)-Ia are enantiomerically stable in solution at 110 °C, they were obtained with only 64% ee and 48% ee, respectively, because of racemization occurring both at the demethylation/esterification and at the crown formation stages of the synthesis. Solution synthesis provided access to: (i) a number of [20-C-6]-Bip/Gly peptides up to the pentapeptide Boc-[20-C-6]-Bip-Gly-Gly-[20-C-6]-Bip-Gly-OMe (RR,SS)- and (RS,SR)-Va as a mixture of two racemic isomers, and (h) the heptapeptide Boc-[20-C-6]-Bip-(Aib)(6)-OtBu (S)-VI. Conformational analysis of (S)-VI by FT-IR absorption and H-1 NMR indicated a high degree of folding, with spectral patterns typical of a 3-10-helical peptide. The absolute configuration of the [20-C-6]-Bip residue was correlated with the CD pattern in the 200-300 nm region. (literal)
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