We describe a single-step procedure to lock the geometry of a oligopeptide by cyclization of hybrid alfa/beta-dipeptide already present in the sequence. Indeed, the hybrid sequence composed of a alfa-amino acid and a alfa-hydroxy-beta2-amino acid, or alfa-hydroxy-beta2,2-amino acid, or alfa-hydroxy-beta2,3-amino acid, etc, readily underwent cyclization to 5-aminomethyloxazolidine-2,4-dione rings (Amo) dipeptide-mimetic scaffolds by treatment with a carbonate and a catalytic amount of base. From a structural point of view, Amo can be regarded as a novel constrained beta2-amino acid. Among the beta-amino acids, the beta2-amino acids are less synthetically feasible with respect to their beta3-counterparts. Moreover, the cyclic structure of Amo, achieved through acylation of the backbone nitrogen atom, embraces two consecutive amino acids, therefore introducing a global constraint of C(i)-N(i+1) type in the sequence. This kind of short-range cyclization can significantly reduce the conformational space accessible to the peptide segment in which they are incorporate. In this context, the Amo ring can be regarded as a novel beta2-homo analogue of a Freidinger lactam
Hybrid alfa/beta-dipeptide scaffolds as inductors of constrained conformations
DE MARCO, ROSSELLA;GRECO, ARIANNA;GENTILUCCI, LUCA
2014
Abstract
We describe a single-step procedure to lock the geometry of a oligopeptide by cyclization of hybrid alfa/beta-dipeptide already present in the sequence. Indeed, the hybrid sequence composed of a alfa-amino acid and a alfa-hydroxy-beta2-amino acid, or alfa-hydroxy-beta2,2-amino acid, or alfa-hydroxy-beta2,3-amino acid, etc, readily underwent cyclization to 5-aminomethyloxazolidine-2,4-dione rings (Amo) dipeptide-mimetic scaffolds by treatment with a carbonate and a catalytic amount of base. From a structural point of view, Amo can be regarded as a novel constrained beta2-amino acid. Among the beta-amino acids, the beta2-amino acids are less synthetically feasible with respect to their beta3-counterparts. Moreover, the cyclic structure of Amo, achieved through acylation of the backbone nitrogen atom, embraces two consecutive amino acids, therefore introducing a global constraint of C(i)-N(i+1) type in the sequence. This kind of short-range cyclization can significantly reduce the conformational space accessible to the peptide segment in which they are incorporate. In this context, the Amo ring can be regarded as a novel beta2-homo analogue of a Freidinger lactamI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
