Philippe Picard

Transposition des oxirannes-ethanols par l'intermediaire d'alcoxyetains

Abstract Oxiraneethoxytributyltins prepared from the corresponding oxiraneethanols, on heating at ∼ 200° gave, after demetalation with isophthallic acid, 2-oxetanemethanols and/or 3-oxolanols. As appears from about thirty rearrangements the choice between oxetane and oxolane formation is dependent on: (1) the relative degree of substitution of the oxirane ring; cyclization occuring predominantly at the more substituted carbon; and (2) the configuration of the oxirane ring, when both its ends are equally substituted; cis form being more suitable for generation of the smaller ring. The reaction is shown to proceed with inversion of configuration at the site of oxygen attack. The results of attempts to perform the rearrangement in dilute-phase or through alkaline metal alkoxides in various media support the conclusion that there is a large contribution by electrophilic assistance to the oxirane opening. Such assistance can be efficiently provided by a tin atom in a push-pull mechanism which accomodates all the facts. The present method of oxiraneethanol rearrangement may offer a convenient route to functional oxetanes.

Transposition des oxirannes-ethanols par l'intermediaire d'alcoxyetains. Influence de la configuration de l'oxiranne

Abstract The transposition of oxirane-ethanols, through alkoxytin compounds, into oxetane-2-methanols and/or oxolan-3-ols (tetrahydrofuran-3-ols) is dependent upon the oxirane configuration. Cis configuration is more suitable for the formation of the smallest ring. Steric hindrance is not sufficient enough to explain the results.

Covalent modification of a melanoma-derived antigenic peptide with a natural quinone methide. Preliminary chemical, molecular modelling and immunological evaluation studies

A LigandFit shape-directed docking methodology was used to identify the best position at which the melanoma-derived MHC class-I HLA-A2-binding antigenic peptide ELAGIGILTV could be modified by attaching a small molecule capable of fitting at the interface of complementary determining regional (CDR) loops of a T-cell receptor (TCR) while triggering T-cell responses. The small molecule selected here for determining the feasibility of this alternative track to chemical alteration of antigenic peptides was the electrophilic quinone methide (+)-puupehenone (), a natural product that belongs to a family of marine metabolites capable of expressing immunomodulatory activities. A preliminary chemical reactivity model study revealed the efficacy of the thiol group of a cysteine (C) side-chain in its nucleophilic addition reaction with in a regio- and diastereoselective manner. The best TCR/HLA-A2 ligand [i.e., ELAGCGILTV-S-puupehenol ()] then identified by the LigandFit docking procedure was synthesized and used to pulse HLA-A2(+) T2 cells for T-cell stimulation. Among the ELAGIGILTV-specific T-cell clones we tested, five of them recognized the conjugate in spite of its low binding affinity for the HLA-A2 molecules. The resulting T-cell stimulation was determined through the intracytoplasmic secretion of IFN-gamma and the percentage of T-cells thus activated. These highly encouraging results indicate that small non-peptidic natural product-derived molecules attached onto the central part of an antigenic peptide can fit at the TCR/HLA-A2 interface with induction of T-cell responses.

Synthesis of new norbornenones with the aminoester group methyl bicyclo [2-2-1] hept 5-ene 7-one 1-amino 2-carboxylates

Abstract Amino norbornenonecarboxylates were synthesized from methyl acrylate and amino butadienecarboxylates. This result is equivalent of amino cyclopentadienones Diels-Alder reaction. Amino butadienecarboxylates were prepared by prototropic transposition of the β-allenic aminoesters.

Captodative dienes in cycloaddition conditions: synthesis of new bicyclo (3.2.0) hept-3-ene-2-ones

Abstract Aminobicyclo (3.2.0) heptenones and aminonorbornenones were obtained from methylacrylate or acrylonitrile and captodative dienes. They result from respectively (2+2) and (4+2) cycloadditions.

Immunoreactivity and conformation of the immunodominant domain of HTLV-I envelope surface glycoprotein

The envelope of the human retrovirus HTLV-I (human T-cell leukemia virus type I), like those of other retroviruses, plays an important role in viral infection. One of the major immunodominant domains of HTLV-I surface glycoprotein (gp46), inducing antibody reactions in over 90% of infected individuals, is bounded by amino acids 175 and 199. As compared to HTLV-I prototype strain MT-2, few amino acid substitutions have been described in this region; the most frequently observed is the replacement of a proline by a serine at position 192. In order to investigate the antigenic impact of this variation, we analysed the reactivity of synthetic peptides, harbouring either a proline or a serine residue, towards antibody containing HTLV-I positive sera in enzyme linked immunosorbent assays. The possible influence of this amino acid substitution on the conformational behaviour has been examined by studying the solution structure of two model peptides (corresponding to the 175–199 region) using two-dimensional1H NMR spectroscopy. The results of this work should allow us to find out whether this amino acid substitution has to be taken into account for the design of a future peptide-based vaccine against HTLV-I infection.

GEM-acceptor, donor-disubstituted dienes in cycloaddition facile [1,3] rearrangement of new bicyclo [2.2.1] hept-5-ene-7-ones

Abstract The (4+2) cycloaddition of methyl 1-diethylamino-2-ethyl-1,3-butadiene-1-carboxylate was performed with acrylonitrile. The cycloadduct bridges over to form 1-diethylamino-6-ethyl-bicyclo [2.2.1] hept-5-ene-7-one-2-carbonitrile 3. We demonstrate that this latter product underoges facile [1,3] sigmatropic rearrangement.

Stereoselective Synthesis of Methyl 15,16-Epoxypimarates

Abstract Methyl 15,16-epoxypimarates are stereoselectively obtained from 15-hydroxy-16-tosyl derivatives by an intramolecular substitution

Constrained Refinement Based on NOE and Chemical Shift Information: The Monomer Form of Arginine–Vasopressin‐like Insect Factor

Via the refinement process of the monomer form of an arginine–vasopressin‐like insect factor, the paper analyses the most relevant NMR information to define the solution structure of a flexible peptide. The relative importance of the different NOE constraints is discussed.

A new composite biomaterial — An artificial connective matrix linked to a polyglactine lattice — Used for vascular prosthesis

The covalent association of a new artificial connective matrix with Vicryl lattice is described. The Vicryl offers strength and compliance while the original matrix resembles the natural sub-endothelium of arteries.