Synthèse de phosphoramidates de 2-désoxy-2-iodoglycosyles

Addition of iodazide to acetylated, benzylated, and methoxymethylated glycals yielded 2-deoxy-2-iodoglycosyl azides with 1,2-trans configuration. Stereoselectivity of the reaction favored the manno and talo configurations starting from d-glucal and d-galactal, respectively. With d-xylal derivatives, the stereoselectivity depended on the nature of the substituents. The Staudinger reaction of 2-deoxy-2-iodoglycosyl azides with trimethylphosphite led to the corresponding 2-deoxy-2-iodoglycosyl phosphoramidates in high yield.     

Synthèse des méthyl-2,4,6-tridésoxy-4-trifluoroacétamido-l-hexopyranosides. Accès à de nouvelles anthracyclines

The four diastereoisomeric methyl 2,4,6-trideoxy-4-trifluoroacetamido-l-hexopyranosides have been synthesized. Coupling of the corresponding 1-O-acetyl-3-O-benzoyl-l-lyxo and 1-O-acetyl-3-O-p-nitrobenzoyl-l-arabino derivatives with daunomycinone in the presence of p-toluensulfonic acid as catalyst afforded two new anthracyclines.     

Synthèse des 2-acé-tamido-2-désoxy-6-O-α-et β-D-xylopyranosyl-α-D-glucopyranose

2-Acetamido-2- deoxy-6-O-, -xylopyranosyl-O-D-glucopyranose has been synthesized in crystalline form by condensation of 2,3,4-tri-O-acetyl-α-D-xylopyranosyl chloride (1) with benzyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranoside (2), followed by O-deacetylation and catalytic hydrogenation. Condensation of 2 with 2,3,4-tri-O-chlorosulfonyl-β-D-xylopyranosyl chloride, followed by dechlorosulfonylation and acetylation, gave benzyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-6-O-(2,3,4-tri-O-acetyl-α-D-xylopyranosyl)β-D-glucopyranoside in crystalline form. O-Deacetylation, followed by catalytic hydrogenation, gave 2-acetamido-2-deoxy-6-O-α-D-xylopyranosyl-α-D-glucopyranose in crystalline form.     

Synthèse de l'acide 5-acétamido-3,5-didésoxy-4-O-méthyl- d-glycéro-d-galacto-2-nonulosonique (acide 4-O-méthyl-N-acétylneuraminique). Partie II

3-Acetamido-3-deoxy-4,5:6,7-di-O-isopropylidene-d-glycero-d-galacto-heptose diethyl dithioacetal was transformed into 3-acetamido-3-deoxy-4,5:6,7-di-O-isopro-pylidene-2-O-methyl-aldehydro-d-glycero-d-galacto-heptose after O-methylation followed by desulfuration. A Wittig reaction with an excess of [ethoxy(ethoxycarbonyl)-methylene]triphenylphosphorane in the presence of benzoic acid gave a mixture of ethyl 5-acetamido-3.5-dideoxy-2-O-ethyl-6,7:8,9-di-O-isopropylidene-4-O-methyl-d-glycero-d-galacto-non-2-enonate (23 %) and the d-glycero-d-talo (22 %) isomer. An ethoxymercuration-demercuration reaction, followed by acid hydrolysis, converted the former into ethyl 4-O-methyl-N-acetylneuraminate and the latter into the C-4 stereoisomer. 4-O-Methyl-N-acetylneuraminic acid was then obtained in crystalline form, and its structure ascertained by mass spectrometry and ¹H- and ¹³C-nuclear magnetic resonance.     

Interactions glycanne-protéine. Synthése des 4-méthylombelliféryl-(2-acétamido-2-désoxy-β-D-glucopyranoside), -DI-N-acétyl-β-chitobioside et -tri-N-acétyl-β-chitotrioside. Interaction de ces osides avec le lysozyme

4-Methylumbelliferyl 2-acetamido-2-deoxy-β-D-glucopyranoside, 2-acetamido-4-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-2-deoxy-β-D-glucopyranoside (di-N-acetyl-β-chitobioside), and O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→4)-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranoside (tri-N-acetyl-β-chitotrioside) were obtained in good yield from the corresponding peracetylated glycosyl chlorides by condensation with the sodium salt of 4-methylumbelliferone in N,N-dimethylformamide. The trisaccharide glycoside is hydrolyzed by lysozyme and is, therefore, a convenient substrate for this enzyme; the 4-methylumbelliferone produced can be determined by the increase of the fluorescence intensity at 442 nm. The intensity of the fluorescence of 4-methylumbelliferyl tri-N-acetyl-β-chitotrioside is enhanced upon binding with lysozyme without modification of the position of the absorption maximum. The binding constant and the rate of hydrolysis of the trisaccharide glycoside by lysozyme are higher than those obtained with p-nitrophenyl tri-N-acetyl-β-chitotrioside.     

Synthèse et réactivite du méthyl-2-O-benzoyl-3-bromo-3,6-didésoxy-α-l-altropyranoside et du méthyl-2-O-benzoyl-3-bromo-3,6-didésoxy-4-O-méthyl-α-l-altropyranoside

Methyl 2-O-benzoyl-3-bromo-3,6-dideoxy-α-l-altropyranoside (4) and methyl 2-O-benzoy]-3-bromo-3,6-dideoxy-4-O-methyl-α-l-altropyranoside (5) have been prepared from methyl-α-l-rhamnopyranoside, respectively, in 2 and 3 steps. Reduction of 4 with lithium aluminium hydride followed by acid hydrolysis afforded the 3,6-dideoxy-l-arabino-bexose (l-ascarylose). The anhydro sugars 8 and 9 have been used as intermediates in the stereoselective synthesis of 6-deoxy-3-O-methyl-l-altropyranose (l-vallarose) and of 3-amino-3-degxy-l-altro sugars. Under azidolysis conditions, and according to the temperature, 5 gave unsaturated sugars such as 20 and the derived 26, or azido compounds such as 21 and 24, and the derived sugar methyl 2-amino-2,3,6-trideoxy-α-l-threo-hexopyranosid-4-ulose (25).     

Prostasomes, dérivés actifs de l’oxygène et sperme humain

Prostasomes are particular lipid vesicles secreted by the human prostate and found in the semen. No specific action has yet been attributed to prostasomes, but they appear to act at various levels. For example, prostasomes enhance sperm motility in vitro and participate in the immunomodulation properties of seminal plasma. Excessive production of reactive oxygen species (ROS) in human semen has a negative influence on the functional capacities of spermatozoa. The presence of leukocytes in semen is associated with increased production of ROS that can be harmful to sperm cells, under certain conditions. Previous results tend to suggest a possible role of prostasomes on ROS production in human semen. After reviewing the literature concerning the structural and functional characteristics of prostasomes and the role of ROS in human semen, we report our results concerning the influence of prostasomes on ROS production and the consequences on semen. We have demonstrated that prostasomes exert an antioxidant function in human semen. This function is effective both on polymorphonuclear neutrophils and on sperm cells. The mechanism of action of prostasomes is unusual, as they act on ROS production mainly on the plasma membranes of neutrophils. They induce a decrease of NADPH-oxidase activity associated with rigidification of the plasma membrane. Prostasomes protect the functional capacities of spermatozoa during an oxidative stress created by the presence of NADPH in the incubation medium.     

Synthèses et réductions de sucres fonctionnels mono et diinsaturés

Attempts to prepare 1,2:5,6 and 2,3:5,6 di-unsaturated sugars starting from 3,4,6-tri-O-acetyl-1,5-anhydro-1,2-dideo xy-d-arabino-hex-1-enitol or from ethyl 4,6-di-O-acetyl-1,5-anhydro-2,3-dideoxy-α-d-erythro-hex-2-enopyranoside led to 1,5-anhydro-1,2,6-trideoxy-l-threo-hex-5-enitol and its 3,4-diacetate. Hydrogenation and hydrogenolysis of the unsaturated chloro and fluoro derivatives afforded 1,5-anhydro-1,2,6-trideoxy-d-arabino-hexitol and ethyl 4-O-acetyl-2,3,6-trideoxy-α-d-erythro-hexopyranoside.     

Synthèse d'ARN et de protéines dans des disques de patte de drosophile cultivés in vitro

Résumé Des disques imaginaux de patte, prélevés dans des larves de fin de 3e stade de drosophile, ont été cultivés dans le milieu M de Mandaron, en l'absence d'hormone ou en présence soit d'- soit de -ecdysone. L'incorporation de précurseurs marqués (³H-uridine,³H-leucine ou³H-proline) a été étudiée en fonction du stade de développement des disques.En l'absence d'hormone de mue, l'incorporation d'uridine décroît dès que les disques ont été explantés; l'incorporation de leucine et de proline ne décroît que 6 à 12 heures après l'explantation.- et -ecdysone stimulent l'incorporation des trois précurseurs; toutefois celle-ci varie en fonction du développement morphologique du disque.Les maxima et les minima d'incorporation d'uridine précèdent dans le temps ceux de la leucine et de la proline.Les maxima d'incorporation peuvent être mis en rapport avec des évènements morphologiques marquants du développement: évagination, sécrétion des cuticules nymphale et maginale.Il n'y a pas de différences significatives d'incorporation d'uridine en présence d'-ecdysone ou de -ecdysone; en revanche les maxima d'incorporation de leucine et de proline sont plus élevés en présence d'-ecdysone que de -ecdysone.Ces résultats montrent que l'-ecdysone—et à un degré moindre la -ecdysone—peuvent induire les synthèses de macromolécules nécessaires au développement des appendices in vitro.

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RNA and protein synthesis inDrosophila leg discs cultured in vitro

Summary Imaginal leg discs from late third instarDrosophila larvae were cultured in Mandaron's medium without hormone or with -ecdysone or -ecdysone. Incorporation of labelled precursors (tritiated uridine, tritiated leucine or tritiated proline) was studied as a function of the stage of in vitro disc development.In the absence of moulting hormone, uridine incorporation decreased as soon as the discs were explanted; leucine and proline incorporation however began to decrease only after 6 to 12 h.- and -ecdysone stimulated the incorporation of all three precursors; however the rate of the incorporation varied as a function of the morphological disc development.The maxima and minima of uridine incorporation preceeded in time those of proline and leucine incorporation.The peaks of incorporation were coincident with salient morphological events of development: evagination, secretion of pupal and imaginal cuticles.There were no significant differences in uridine incorporation in the presence of -ecdysone or -ecdysone. Leucine and proline incorporation maxima however were significantly higher in the presence of -ecdysone than of -ecdysone.The results show that -ecdysone—and to a lesser extent also -ecdysone—can induce the macromolecular syntheses required for the development of the appendage in vitro.

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Ce travail a été réalisé avec l'aide du CNRS (Action thématique programmée «Différenciation cellulaire», contrat n^o A 6554324)

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Ce mémoire représente une partie de la thèse qui sera soutenue par l'auteur devant l'Université Scientifique et Médicale de Grenoble     

Synthèse et étude R.M.N. de disaccharides et trisaccharides dans la série du l-rhamnose

Various di- and tri-saccharides containing l-rhamnose were synthesized by condensation of 2,3,4-tri-O-acetyl- or 2,3,4-tri-O-benzoyl-α-l-rhamnopyranosyl bromide with an unblocked glycopyranoside. The determination of the anomeric configuration of l-rhamnose saccharides by n.m.r. is difficult because structure has a greater effect on the spectra than does configuration. The α and β configurations and the position of the substitution may be assigned from the chemical shifts of H-5 and CH₃. In all the compounds having a β configuration, a shielding of the methyl group and a deshielding of the H-5 proton have been observed as compared to the compounds having an α configuration. The H-5 proton and the methyl group of peracetylated, (1→3)-linked α-l derivatives always resonate at higher fields than the corresponding protons of (1→6)-linked α-l derivatives.     

Synthèse et réactivité vis-à-vis de réactifs nucléophiles des méthyl-3,4-anhydro-2,6-didésoxy-α- et -β-l-lyxo- et -ribo-hexopyranosides

The ring-opening reactions of methyl 3,4-anhydro-2,6-dideoxy-α- and -β-l-lyxo- and -ribo-hexopyranosides with sodium azide, ammonia, methyl- and dimethylamine, and sodium methoxide were studied. Regioselectivity is explained in terms of steric and conformational factors.     

Synthèse du 4-O-[(s)-1-carboxyéthyl]-d-glucose et de son isomère (R)

Alkylation of benzyl 2,3,6-tri-O-benzyl-β-D-glucopyranoside in N,Ndimethyl formamide with (R)-2-chloropropionic acid gave crystalline benzyl 2,3,6-tri-O-benzyl-4-O-[(S)-carboxyethyl]-β-D-glucopyranoside. After hydrogenolysis of the benzyl group 4-O-[(S)-D-carboxyethyl]-D-glucose was obtained which lactonized very easily. Treatment of benzyl 2,3,6-tri-O-benzyl-4-O-[(S)-1-carboxyethyl]-β-D-glucopyranoside with diazomethane gave cristalline benzyl 2,3,6-tri-O-benzyl-4-O-[(S)-1-(methoxycarbonyl)ethyl]-β-D-glucopyranoside, which was reduced with lithium aluminium hydride to crystalline benzyl 2,3,6-tri-O-benzyl-4-O-[(S)-1-(hydroxymethyl)ethyl]-β-D-glucopyranoside After hydrogenolysis of the benzyl groups 4-O-[(S)-1-(hydroxymethyl)ethyl]-D-glucose was obtained. A similar sequence of reactions was performed with (S)-2-chloropropionic acid.     

Synthèse biostratigraphique du plio-pléistocène de Guadix-Baza (Province de Granada,Sud-Est de l'Espagne)

In the Guadix-Baza basin, a continental sequence 0214 ranging from the Upper Miocene (Upper Turolian) to the Middle Pleistocene (Cromerian) has been established. An essay of biozonation by means of the Rodent succession is proposed, based on the following biozones: Trilophomys castroi, Mimomys occitanus, Mimomys cappetai, Mimomys cf. reidi, Mimomys ostramosensis, Allophaiomys pliocaenicus, Mimomys savini and Arvicola cantiana.     

Diminution de la capacité de surfusion au cours de l'embryogenèse et du développement larvaire chez un coléoptère

Potential cold resistance of non-diapause eggs and first instar larvae of Osmoderma eremita (Coleoptera, Cetoniidae, Trichiinae) during embryogenesis and post-embryonic growth was assessed by measuring individual supercooling points (SCP): sterile eggs had a mean SCP of −24.3 ± 2.0 °C; fertilized newly laid eggs a mean SCP of −23.4 ± 3.2 °C and eggs about to hatch a mean SCP of −9.2 ± 2.9 °C. Water absorption by fertilized eggs is a necessary requirement for the development of the embryo and results in an increase in weight and water content: fertilized newly laid eggs had a mean fresh weight of 10.687 ± 1.072 mg and a mean water content (expressed as a percentage of the dry weight) of 79.5 ± 10.83%; eggs about to hatch had a mean fresh weight of 19.127 ± 3.183 mg and a mean water content of 250.10 ± 74.15%. The ex-ovo larvae, hatched 30 days after oviposition, had a mean SCP of −10.1 ± 3.6 °C (no significant difference with eggs about to hatch) and had gained in weight (24.845 ± 3.911 mg) and in water content (499.72 ± 55.49%). Feeding 1st instar larvae had a decreased supercooling ability (mean SCP = −5.7 ± 0.4 °C) whereas their mean fresh weight (99.858 ± 53.091 mg) and mean water content (665.83 ± 82.74%) increased. The eggs and larvae of O. eremita are freezing intolerant. Before overwintering, all larvae switch to being freezing tolerant and can survive ice formation in their tissues and body fluids, whereas their mean SCP stays at around −5 °C. However, recent experiments in the winter of 1996 have shown that frozen larva mortality does occur at temperatures lower than about −12 °C.