Urethane N-carboxyanhydrides from beta-amino acids.

A general method has been developed for the synthesis of N-tert-butyloxycarbonyl N-carboxyanhydrides from beta-amino acids using Vilsmeier complex. These beta-UNCA are stable, and the reactivity with different nucleophiles (alcohol, amine, lithium enolate) was studied.

Chemoenzymatic synthesis of surfactants from carbohydrates, amino acids, and fatty acids.

The chemoenzymatic synthesis of new surfactants is reported; they were prepared from unprotected carbohydrates, amino acids, and fatty acids. This study pointed out the factors that govern the possibility to enzymatically bind the carbohydrate to the amino acid.

Chemo-enzymatic synthesis of new non ionic surfactants from unprotected carbohydrates.

The synthesis of new non ionic surfactants is reported. They were prepared from unprotected carbohydrates, amino acids, and fatty alcohols. These modules were linked by enzymatic esterification and transesterification reactions catalysed by lipases and proteases in organic media.

Synthesis of phosphonic analogues of 4-hydroxyproline and 5-hydroxypipecolic acid.

Interest in non-natural amino acids is growing because of their potential biological activity. We describe in this paper, a synthesis of phosphonic analogues of 4-hydroxy proline and 5-hydroxy pipecolic acid.

Diastereoselective synthesis of non-proteinogenic alpha-amino acids.

The synthesis of enantiomerically pure azatyrosine, tribromophenylalanine and trichlorophenylalanine is described, using two methods, diastereoselective alkylation and (or) diastereoselective protonation of chiral enolates.

Synthesis of biheterocyclic alpha-amino acids.

We report here the synthesis of biheterocyclic alpha-amino acids by 1,3 dipolar cycloaddition of acetylenic compounds on alpha-azido alpha-amino esters.

Some of the amino acid chemistry going on in the Laboratory of Amino Acids, Peptides and Proteins.

Some of the chemistry of amino acids going on in our laboratory (Laboratoire des Amino acides Peptides et Protéines) is described as well as some mass spectrometry methodology for their characterization particularly on solid supports. Several aspects are presented including: (i) the stereoselective synthesis of natural and unnatural amino acids using 2-hydroxypinan-3-one as chiral auxiliary; (ii) the stereoselective synthesis of natural and unnatural amino acids by deracemization of alpha-amino acids via their ketene derivatives; (iii) the synthesis of alpha-aryl-alpha-amino acids via reaction of organometallics with a glycine cation; (iv) the diastereoselective synthesis of glycosyl-alpha-amino acids; (v) the synthesis of beta-amino acids using alpha-aminopyrrolidinopiperazinediones as chiral templates; (vi) the reactivity of urethane-N-protected N-carboxyanhydrides. To characterize natural and non natural amino acids through their immonium ions by mass spectrometry, some methodology is also described.

Synthesis and characterization of a new biotinylated gramicidin.

A new linear gramicidin analog bearing a biotinyl group grafted on C-terminal part was designed to study ligand-receptor interactions. The C-terminal alcohol in the native peptide was first replaced by an amino group. Then the peptide was synthesized on a polystyrene resin functionalized by the 2-chlorotrityl chloride following a biotinylation performed in solution. This new N'-biotinyl-(EDA)15-Gramicidin A was reconstituted in planar lipid bilayers and exhibited channel activities similar to those of natural gramicidin, with unitary conductance value about 30 ps in 1 M KCl. Furthermore this ionophore activity was quenched by addition of streptavidin in the surrounding medium. Our system is an outstanding tool for monitoring ligand-receptor interactions and could be used for designing a new biosensor.

Synthesis of beta-tetrazolyl DL-alanine derivatives.

Interest in non-natural alpha-amino acids is growing because of their potential biological activity. We describe, in this paper, a synthesis of beta-tetrazolyl alpha-amino esters by action of 5-aryl tetrazoles, 2, on N-benzyloxycarbonyl di-dehydro methylalaninate, 3.

Synthesis and biological activity of glutamic acid derivatives.

In order to develop new specific glutamate analogues at metabotropic glutamate receptors, Diels-Alder, 1-4 ionic and radical reactions were performed starting from (2S)-4-methyleneglutamic acid. Preliminary pharmacological evaluation by measuring IP accumulation using rat forebrain synaptoneurosomes has shown that (2S)-4-(2-phthalimidoethyl)glutamic acid (3a), (2S)-4-(4-phthalimidobutyl)glutamic acid (3b) and 1-[(S)-2-amino-2-carboxyethyl]-3,4-dimethylcyclohex-3-ene-1-carbox ylic acid (8) presented moderate antagonist activities.

Specific recognition of a tetrahedral phosphonamidate transition state analogue group by a recombinant antibody Fab fragment.

In order to obtain antibodies able to catalyse a peptide synthesis, a naive combinatorial library of human Fab antibody fragments was screened with the phosphonamidate transition state analogue of the reaction. Several Fab fragments were able to bind the analogue. Competitive binding studies performed with molecules containing representative parts of the hapten showed that two Fabs were able to recognize specifically the tetrahedral phosphorus present in the hapten.

Neuroexcitatory amino acids: 4-methylene glutamic acid derivatives : Short Communication.

A short synthesis of 4-methylene glutamic acid was achieved. Under thermal conditions the corresponding anhydride reacted with 2,3 dimethylbutadiene to afford the corresponding DIELS-ALDER adduct in good yield. L-4-methylene glutamic acid essentially acts on glutamate metabotropic receptors and is as potent as L-Glu in producing IPs.

Asymmetric synthesis ofα-substitutedß-amino acids using aß-alanine derivative with two chiral handles.

Enantiomerically pureα-substitutedß-amino acids have been synthesized, the key step being the diastereoselective alkylation of aß-alanine derivative with two chiral handles (1S,2R,5S)-menthyl N-[(1S,2S,5S)-2-hydroxypinan-3-ylidene]ß-alaninate.

Sulfenylation of chiral Schiff bases.

The purpose of this study was to examine the conditions of sulfenylation reactions of chiralα-amino esters Schiff bases to protect the chirality in theα-position.

Enzymatic peptide synthesis by new supported biocatalysts.

It is well known that proteases can be successfully used for peptide synthesis in aqueous medium or in water-containing organic solvents. Copolymerized of acrylated derivatives ofα-chymotrypsin and polyethylene glycol (PEG) have been prepared and used as biocatalysts for the synthesis of model peptides in organic solvents containing a very low quantity of water. Trypsin has been similarly treated and used as a new biocatalyst particularly for the coupling of non-specific substrates.

New antitumoral cyclopeptides.

Chlamydocin is a powerfulin vitro antitumoral agent, quickly inactivatedin vivo. A series of cyclic tetrapeptides related to chlamydocin or HC toxin and bearing a bioactive alkylating group on anε-amino-lysyl function have been examined for their antitumoral activity on L1210 and P388 murine leukemia cell lines. One analog was found to be potent at inhibiting L1210 cell proliferation and had a higher therapeutic index than the reference compound bis-ß-chloroethylnitrosourea on thein vivo P388-induced leukemia model.

Antitumoral cyclic peptide analogues of chlamydocin.

A series of cyclic tetrapeptides bearing the bioactive alkylating group on an epsilon-amino-lysyl function have been examined for their antitumoral activity on L1210 and P388 murine leukemia cell lines. One analogue belonging to the chlamydocin family and bearing a beta-chloroethylnitrosourea group was found to be potent at inhibiting L1210 cell proliferation and had a higher therapeutic index than the reference compound bis-beta-chloroethylnitrosourea (BCNU) on the in vivo P388-induced leukemia model.

Asymmetric synthesis ofα-aminophosphonic acids.

The enantiospecific synthesis of severalα-aminophosphonic esters starting from enantiomerically pure derivatives of phosphonic analogues of homoserine is reported.