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An Improved Synthesis of 3,4‐(Aminomethano)proline and Its Incorporation into Small Oligopeptides
Author(s) -
Brackmann Farina,
Colombo Noemi,
Cabrele Chiara,
de Meijere Armin
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200600404
Subject(s) - chemistry , oligopeptide , peptide synthesis , amino acid , protecting group , proline , peptide , stereochemistry , circular dichroism , aldehyde , methanol , solvent , residue (chemistry) , bicyclic molecule , nuclear magnetic resonance spectroscopy , combinatorial chemistry , organic chemistry , catalysis , biochemistry , alkyl
Starting from the readily available Garner aldehyde, a new synthesis of diastereomerically and enantiomerically pure 3,4‐(aminomethano)prolinol (2 R ,1′ S ,3 S ,4 S )‐ 17 has been developed using simple and easily scalable transformations. The protected diamino alcohol (2 R ,1′ S ,3 S ,4 S )‐ 17 has been shown to be an appropriate compound for the exchange of protecting groups. Final Jones oxidation furnished the correspondingly protected diamino acids in high yields. The newly synthesized Fmoc/Boc‐protected 3,4‐(aminomethano)proline (Amp) derivatives, which are proline mimics as well as bicyclic γ‐amino acids, depending on the orthogonal protecting group pattern, were employed for solid‐phase peptide synthesis with the Fmoc strategy. Thus, the features of Amp as a γ‐amino acid residue (γ‐Amp) were investigated in the preparation of alternating α/γ‐amino acid sequences. The obtained highly homogeneous products were characterized by circular dichroism spectroscopy. The fact that the dichroic properties of the α/γ‐oligopeptides were independent from the solvent used (water or methanol) suggests the presence of a preferred conformation. These results are encouraging for the development of foldamers based on γ‐Amp units. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)