Marzia Villa

Pyroglutamic acid as a pseudoproline moiety: a facile method for its introduction into polypeptide chains

Abstract The acylation of benzyl ( S )-pyroglutamate is reported by reaction with the pentafluorophenyl ester of protected alanine and threonine. The 1 H NMR analysis of the acylated products shows that the α hydrogens of the protected amino acids are very deshielded. This effect is due to the presence of the carbonyl of the lactam ring and shows that the peptide bond is in the trans conformation. The deprotection of the amino acids is also reported.

Diastereoselective addition of higher order cuprates and zinc-copper reagents to imines derived from (S)-1-phenylethylamine

Abstract The diastereoselective addition of higher order (H.O.) cuprates and zinc-copper reagents to aliphatic and aromatic chiral imines derived from ( S )-1-phenylethylamine was examined. Aliphatic chiral imines react with (Allyl) 2 CuCNLi 2 and (n-Bu) 2 Cu(CN)Li 2 in the presence of BF 3 ·Et 2 O and Me 3 SiCl in high diastereoselection, while c-C 6 H 11 Cu(CN)ZnI and AllylCu(CN)ZnBr afford chiral amines in comparable yields without additives. Moreover the synthesis of a key intermediate towards a δ-amino-acid was reported.

Solution phase library of perhydrooxazin-4-ones

Abstract A general approach to the solution phase parallel synthesis of perhydrooxazin-4-ones, which allows the preparation of milligram quantities of each individual member, is reported. An efficient purification method, using as “Sequestration Enabling Reagent” (SER) aminomethylpolystyrene resin in the presence of trimethylorthoformate is also described.

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.

(αMe)Hyv: chemo-enzymatic synthesis, and preparation and preferred conformation of model depsipeptides

By a chemo-enzymatic approach we performed a large-scale, stereoselective synthesis of the Cα-methylated α-hydroxy acid L-(αMe)Hyv. We also prepared model depsipeptides based on this sterically demanding residue in combination with the α-amino acids L-Ala, L-Val, and Aib. From solution (FT-IR absorption and 1H NMR) and crystal-state (X-ray diffraction) conformational analyses we found that L-(αMe)Hyv forces depsipeptides to fold into right-handed β-turn/helical structures by analogy with the reported propensity of L-(αMe)Val, its α-amino acid counterpart.