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Tandem Tetrahydroisoquinoline‐4‐carboxylic Acid/β‐Alanine as a New Construct Able To Induce a Flexible Turn
Author(s) -
Bucci Raffaella,
Bonetti Andrea,
Clerici Francesca,
Contini Alessandro,
Nava Donatella,
Pellegrino Sara,
Tessaro Davide,
Gelmi Maria Luisa
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201701045
Subject(s) - enantiopure drug , tetrahydroisoquinoline , chemistry , enantiomer , carboxylic acid , turn (biochemistry) , amino acid , alanine , stereochemistry , covalent bond , combinatorial chemistry , enantioselective synthesis , organic chemistry , catalysis , biochemistry
Tetrahydroisoquinoline‐4‐carboxylic acid, a constrained β 2 ‐amino acid named β‐TIC, was synthesised for the first time in enantiopure form. The biocatalytic route applied herein represents one of the few successful examples of enzymatic resolution of β 2 ‐amino acids. Model tetrapeptides, namely, Fmoc‐ l ‐Ala‐β‐TIC‐β‐Ala‐ l ‐Val‐OBn (Fmoc=fluorenylmethyloxycarbonyl, Bn=benzyl), containing both isomers of β‐TIC, were prepared. Both computational and NMR spectroscopy studies were performed. A reverse‐turn conformation was observed in the case of ( R )‐β‐TIC enantiomer that was obtained in 99 % enantiomeric excess by enzymatic resolution. The β‐TIC/β‐Ala construct represents the first example of a flexible turn mimetic containing a cyclic and an acyclic β‐amino acid. Furthermore, the presence of an aromatic ring of β‐TIC could facilitate non‐covalent interactions to increase the potential of this scaffold for the preparation of protein–protein interaction modulators.