Gianluigi Luppi

β-Pseudopeptide foldamers. The homo-oligomers of (4R)-(2-oxo-1,3-oxazolidin-4-yl)-acetic acid (D–Oxac)

A total synthesis in solution and a conformational analysis of the homo-oligomers of (4R)-(2-oxo-1,3-oxazolidin-4-yl)-acetic acid (D-Oxac) to the tetramer level are described. As the D-Oxac building block contains both an oxazolidin-2-one and a beta-amino acid group, it may represent a new type of conformationally constrained tool for the construction of beta-pseudopeptide foldamers. A conformational investigation using NMR and an extensive, unconstrained analysis with a Monte Carlo search to the octamer level, both in water and in chloroform, showed that these homo-oligomers tend to fold in a regular helical structure in a competitive solvent, such as water. Since aqueous solutions are of major relevance for biological systems, these molecules are good candidates for application to these environments.

Introduction of 4(S)-oxazolidineacetic acid, 2-oxo (D-Oxac) motif in a polypeptide chain: synthesis and conformational analysis

A four step synthesis of 4(S)-oxazolidineacetic acid, 2-oxo benzyl ester (D-Oxac-OBn) from L-Asp-OH in 45% overall yield is reported. The formation of by-products is completely avoided, by microwave irradiation and by the use of caesium carbonate as base. Moreover the synthesis and IR and 1H NMR conformational analysis of the tetramers Boc-L-Val-D-Oxac-L-Ala-OBn and Boc-L-Val-D-Oxac-Aib-L-Ala-OBn in solution is reported.

Atom Economic and Highly Syn‐selective Prolinamide‐Catalyzed Cross‐aldol Addition of Hydroxyacetone to Aromatic Aldehydes

Abstract The highly selective cross‐aldol addition of hydroxyacetone (HA) to p‐nitro and m‐nitrobenzaldehyde is reported; the reaction is catalyzed by three different di‐ or tripeptides all containing D‐Pro in the N‐terminal position and one or two residues of β3‐homophenylglycine (β3‐hPhg): H‐D‐Pro‐(R)‐β3‐hPhg‐OBn, H‐D‐Pro‐(R)‐β3‐hPhg‐(S)‐β3‐hPhg‐OBn and H‐D‐Pro‐[(S)‐β3‐hPhg]2‐OBn. Several reaction conditions have been tested, always in the absence of a protecting group on the HA hydroxyl. This reaction affords the desired compounds with complete regioselectivities being the other regioisomer completely avoided. Furthermore high enantioselectivities and satisfactory diastereoselectivities, always favouring the syn diastereoisomers, were obtained. The stereochemistry of the diols was further confirmed by the analysis of the 1H NMR spectrum of the corresponding carbonates, obtained by reaction of the syn/anti mixtures with triphosgene in presence of dimethylamino‐pyridine (DMAP).

Development of new calcium receptors based on oxazolidin-2-ones containing pseudopeptides.

With the aim of designing a new calcium receptor, the synthesis and the conformational analysis of a small library of dipeptides having the general formula Ac-Oxx-L-Xaa-OBn [Oxx = L-Oxd, (4S,5R)-4-methyl-5-carboxyoxazolidin-2-one; D-Oxd, (4R,5S)-4-methyl-5-carboxyoxazolidin-2-one; or D-Oxac (4R)-(2-oxo-1,3-oxazolidin-4-yl)-acetic acid] is reported. Ac-L-Oxd-L-Ala-OBn was identified as the most promising compound by MS-ESI analysis and this outcome was confirmed by photoluminescence spectroscopy.