Bucci Raffaella, Bonetti Andrea, Clerici Francesca, Contini Alessandro, Nava Donatella, Pellegrino Sara, Tessaro Davide, Gelmi Maria Luisa
DISFARM, Sezione di Chimica Generale e Organica "A. Marchesini", Università degli Studi Milano, Via Venezian 21, 20133, Milano, Italy.
Department of Chemistry, Materials and, Chemical Engineering "G. Natta", Politecnico di Milano, p.za L. da Vinci 32, 20133, Milano, Italy.
Chemistry. 2017 Aug 10;23(45):10822-10831. doi: 10.1002/chem.201701045. Epub 2017 Jul 18.
Tetrahydroisoquinoline-4-carboxylic acid, a constrained β -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 -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.
