Synthesis of the First Axially Dissymmetric, Cα,α-Disubstituted Glycine Containing a Crown Ether Receptor, and the Conformational Preferences of a Model Peptide

✍ Scribed by Jean-Paul Mazaleyrat; Yolaine Goubard; Maria-Vittoria Azzini; Michel Wakselman; Cristina Peggion; Fernando Formaggio; Claudio Toniolo

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 598 KB
• Volume: 2002
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/1099-0690(200204)2002:7<1232::aid-ejoc1232>3.0.co;2-i

✦ Synopsis

Keywords: Atropoisomeric amino acids / Axial chirality / C α,α -disubstituted glycine / Crown compounds / Side-chain modified amino acids Racemic and enantiomerically enriched N α -protected methyl 6-amino-1,11-(20-crown-6)-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-6-carboxylates (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) 2,2Ј-bis(bromomethyl)-6,6Ј-dimethoxy-1,1Ј-biphenyl being used as alkylating agents. Demethylation of the resulting (RS)-, (R)-and (S)-H-[MeO] 2 -Bip-OtBu, followed by esterification and N α -Boc protection, gave (RS)-, (R)-and (S)-Boc-[HO] 2 -Bip-OMe. Cyclization with Cs 2 CO 3 /DMF and pentaethylene glycol ditosylate afforded the crown-carrier C α,α -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