Carlo Siciliano

Quantitative determination of fatty acid chain composition in pork meat products by high resolution 1H NMR spectroscopy

High resolution (1)H NMR spectroscopy was proposed for the determination of the fatty acid chain profile of lipids in pork meat products during ripening. Two typical Mediterranean PDO salami produced in Calabria, a region in the Southern Italy, were chosen as a case of study. Quantitative NMR analysis provided the fatty acid chain profiles of total lipid extracts. The transesterification of total lipid extracts furnished FAME mixtures that enabled quantitation of fatty acid acyl chains in the acylglycerol and FFA portions. In all cases, oleyl chains were predominant, and high amounts of polyunsaturated fatty acid chains were observed. The proposed spectroscopic method allowed also the estimation of the most important nutritional parameters of dry fermented meat products.

Synthesis of 4′-aza analogues of 2′,3′-dideoxythymidine by 1,3-dipolar cycloadditions of nitrones to 1-N-vinyl-thymine

Abstract The title compounds have been obtained by 1,3-dipolar cycloadditions of methylene nitrones, prepared in situ from suitably protected hydroxylamines, to 1- N -vinyl-thymine. The 4′- aza -2′,3′-dideoxyerythrofuranoside ( 4 ), an analogue of 2′,3′-dideoxythymidine, might exhibit antiviral activity.

Binding mode of TMC-95A analogues to eukaryotic 20S proteasome

The complex thermodynamics that govern noncovalent protein–ligand interactions are still not fully understood, despite the exponential increase in experimental structural data available from X‐ray crystallography and NMR spectroscopy. The eukaryotic 20S proteasome offers an ideal system for such studies as it contains in duplicate three proteolytically active sites with different substrate specificities. The natural product TMC‐95A inhibits these proteolytic centers noncovalently with distinct affinities. X‐ray crystallographic analysis of the complexes of the yeast proteasome core particle with this natural inhibitor and two synthetic analogues clearly revealed highly homologous hydrogen‐bonding networks involving mainly the peptide backbone despite the strongly differentiated binding affinities to the three active sites of the 20S proteasome. The natural product and the two analogues are constrained in a rigid β‐type extended conformation by the endocyclic biaryl clamp, which preorganizes the peptide backbone for optimal adaptation of the ligands to the active site clefts and thus favors the binding processes entropically. However, the biaryl clamp also dictates the orientation of the P1 and P3 residues and their mode of interaction with the protein binding subsites. This limitation is optimally solved in TMC‐95A with the conformationally restricted (Z)‐prop‐1‐enyl group acting as P1 residue, at least for the chymotrypsin‐like active site; however, it critically affects the inhibitory potencies of the analogues, thus suggesting the use of less‐rigid endocyclic clamps in the design of proteasome inhibitors that allow for a better presentation of residues interacting with the active site clefts of the enzyme.

Simple and efficient routes for the preparation of isoxazolidinyl nucleosides containing cytosine and 5-methyl-cytosine as new potential anti-HIV drugs

Abstract A rapid and convenient large-scale strategy for the synthesis of some new isoxazolidinyl nucleosides, as potential antiviral drugs, is reported. In particular, a multistep methodology based either on the 1,3-dipolar cycloaddition approach or on a slight modification of the convertible nucleoside concept was exploited in the preparation of 4′-aza-2′,3′-dideoxynucleoside analogues containing cytosine and 5-methyl-cytosine.

Synthesis of D-erythro-sphinganine through serine-derived α-amino epoxides.

A total synthesis of D-erythro-sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol] starting from commercial N-tert-butyloxycarbonyl-L-serine methyl ester is described. The approach is based on the completely stereoselective preparation of an α-amino epoxide obtained by treating a protected L-serinal derivative with dimethylsulfoxonium methylide. The oxirane synthon is obtained with an anti configuration fitting the (2S,3R) stereochemistry of the 2-amino-1,3-diol polar head of D-erythro-sphinganine. The synthetic procedure afforded the target compound in a 68% overall yield based on the initial amount of the starting L-serine material.

A preparation of N-Fmoc-N-methyl-α-amino acids and N-nosyl-N-methyl-α-amino acids

A convenient route for the synthesis of lipophilic N-Fmoc-N-methyl-α-amino acids and N-nosyl-N-methyl-α-amino acids, interesting building blocks to be used for the preparation of N-methylated peptides, is presented. Both nosyl- and Fmoc-protected monomers are accessible, so these compounds can be used in solution as well as in solid phase peptide synthesis. The methodology is based on the use of benzhydryl group to protect temporarily the carboxyl function of N-nosyl-α-amino acids and on the subsequent methylation of the N-nosyl-α-amino acid benzhydryl esters with diazomethane. The benzhydryl esters offer several beneficial features such as simple preparation, stability to methylation and selective deprotection under mild conditions. The overall procedure is highly efficient in that the adopted conditions keep the chiral integrity of amino acid precursors and the process does not require chromatographic purification of the methylated products.

Deprotection/reprotection of the amino group in α-amino acids and peptides. A one-pot procedure in [Bmim][BF4] ionic liquid

This paper presents an efficient one-pot protocol for the sequential deprotection/reprotection of the α-amino group in α-amino acid and dipeptide methyl esters. [Bmim][BF4] is used as the solvent in the entire process. In particular, the use of the ionic liquid allows for rapid and clean removal of the 4-nitrobenzenesulfonyl (nosyl) group and for facile subsequent tert-butyloxycarbonylation of the free α-amino function under very mild conditions. N-Boc-α-amino acid as well as peptide derivatives are isolated in excellent yields, and do not require any further purification. Absolute configurations of the precursors are totally preserved during the process.

Simultaneous extraction and derivatization of amino acids and free fatty acids in meat products

In meat products the contents of free amino acids and free fatty acids are two important parameters used to establish their quality. These compounds play a very important role in defining the sensorial characteristics and acceptability of meat products. An innovative procedure for the measurement of free amino acid and fatty acid contents in meat and meat derivatives was developed. A single experiment can be performed in order to determine simultaneously the free amino acid and free fatty acid profiles. The analytes of interest are rapidly extracted from the meat matrix and derivatized by using methyl chloroformate. This reagent allows the transformation of the two groups of analytes into the corresponding N-methyloxycarbonyl amino acid methyl esters and fatty acid methyl esters that can easily be extracted and sampled for their further identification and quantitation. The measurement of the obtained amino acid and fatty acid derivatives is performed by GC/MS analysis and their concentrations are calculated by using two appropriate internal standards. The main advantage of the proposed protocol is the determination at the same time of two important classes of analytes that are of great importance in food analysis and characterization. Moreover, minimal sample manipulation and preparation, and reduced total extraction times are required to obtain the response with respect to conventional procedures, in which instead the analysis of both the two classes of compounds must be performed separately. The helpfulness of the protocol was tested in the analysis of a cured meat product that is typical of the South of Italy. The optimized protocol successfully allowed the determination of thirteen free amino acids and six free fatty acids, namely those most abundant in the lipid content of the cured meat product under evaluation.

New Strategies for an Efficient Removal of the 9-Fluorenylmethoxycarbonyl (Fmoc) Protecting Group in the Peptide Synthesis

The aluminium trichloride/toluene system is investigated as a novel, unusual and straightforward reagent for the removal of the 9-fluorenylmethoxycarbonyl (Fmoc) protecting group in the solution peptide synthesis. This procedure avoids any undesired side reactions, such as the frequently observed inversion of the amino acid configuration.

Intramolecular displacement of phenylselenone by a hydroxy group: stereoselective synthesis of 2-substituted tetrahydrofurans.

An efficient and stereocontrolled synthesis of 2-substituted tetrahydrofurans has been achieved. The approach employs the asymmetric reduction of γ-phenylseleno ketones obtained by three different procedures that are peculiarly applied to the synthesis of such compounds. Finally, the intramolecular substitution of the phenylselenone residue by the oxygen atom of a hydroxy group gives the tetrahydrofuran ring.