J.-P. Pradere

A novel synthesis of α-d-Galp-(1→3)-β-d-Galp-1-O-(CH2)3NH2, its linkage to activated matrices and absorption of anti-αGal xenoantibodies by affinity columns

Pig organs transplanted into primates are rapidly rejected because of the interaction between Gal alpha(1-->3)Gal epitopes carried by the graft and natural antibodies (anti-alphaGal antibodies) present in the blood of the recipient. This report describes a simplified synthesis of the xenogeneic disaccharide and its linkage to activated gel matrices. The digalactosides alpha-D-Galp-(1-->3)-alpha,beta-D-Galp-OAll were synthesized by the condensation of the trichloroacetimidoyl 2,3,4,6-tetra-O-benzyl-beta-D-galactopyranoside donor with the 3,4-unprotected allyl 2,6-di-O-benzyl-alpha- or beta-D-galactopyranoside acceptor precursor. Deallylation and hydrogenolysis led to the free digalactoside, whereas hydrogenolysis alone resulted in the 1-O-propyl digalactoside. Both products were tested by inhibition ELISA of natural anti-Gal alpha(1-->3)Gal antibodies. The alpha-D-Galp-(1-->3)-beta-D-Galp-OPr was found to be the best inhibitor. Thus, the allyl group of the partially benzylated alpha-D-Galp-(1-->3)-beta-D-Galp-OAll was engineered, via the hydroxy-, the tosyloxy- and the azidopropyl intermediates, into an aminopropyl group amenable to binding to N-hydroxysuccinimide-activated agarose gel matrices in order to obtain specific immunoabsorption columns. Columns made of gel substituted with 5 micromol of disaccharide per milliliter were found efficient for the immunoabsorption of anti-alphaGal antibodies from human plasma.

2-aza-1,3-dienes with electron-releasing substituents at the 1,3 positions. Reagents for the construction of pyridine and pyrimidine derivatives

Abstract New 2-aza-1,3-dienes bearing 1 and 3-donor substituents are prepared from N-thioacylacetamidines through deprotonation of N-ylidene acetamidinium iodides. The 2-aza-3-(dimethylamino)-1-(methylthio)-1-phenylbutadiene (3) is trapped in situ by the residual precursor salt acting as a heterodienophile to give the pyrimidine 5. Substituted 2-aza-1-(dimethylamino)-3-(methylthio) analogues react readily with a variety of electron-deficient dienophiles to yield pyridine or pyrimidine derivatives. The stereochemistry of the hetero Diels-Alder reaction in the cases of dimethyl fumarate and acrylonitrile has been assigned by X-ray diffraction analyses of the resulting tetrahydropyridines and corresponds to an exo selectivity. The number and nature of cycloadducts in the cases of dimethyl acetylenedicarboxylate and phenyl isothiocyanate depend on C-4 substitution. The results obtained from the C-4 unsubstituted azabutadiene 8 are explained by an allylic rearrangement involving the 1,3-migration of dimethylamino group in the primary [4+2] adduct.

Electrochemical reduction of substituted pyridazines: a new access to activated pyrroles

Abstract The electrochemical two electron reduction of pyridazines, substituted by electron withdrawing groups, primarily lead to their corresponding 1,2-dihydro-derivatives. Depending on the nature of the ring substitution, these intermediates can either rearrange into 1,4-dihydro-pyridazines, or undergo electrochemical reduction to give rise to activated pyrroles by a ring contraction reaction with extrusion of nitrogen. Another way of access to the latter has been achieved by a disproportionation reaction of 1,2-dihydro-pyridazines, leading directly to the expected pyrroles and recovery of 50% of pyridazines.

Activated pyrroles from pyridazines: nitrogen extrusion by electroreduction

Abstract The bielectronic electrochemical reduction of pyridazines, substituted by electron-withdrawing groups, leads to their corresponding 1,2-dihydro derivatives. Depending on the nature of the ring substitution, these intermediates can either rearrange into 1,4-dihydropyridazine isomers or be further electrochemically reduced into activated pyrroles.

Thermolysis of Substituted-4H-1,3-Thiazines

Abstract Thermolysis of 4-dimethylamino-2-phenyl-4-substituted 4H-1,3-thiazines leads to thioamide vinylogs or N-methyl 2H-3,4-dihydrothiazine by thermal rearrangement depending on the nature of the substituents.

THIA-1 AZA-3 BUTADIENES SUBSTITUES: ACTION DU CETENE ET DERIVES

Abstract Novel, diversely substituted 1-thia 3-aza butadienes have been prepared and reacted with ketene or its derivatives. Via a general (4 + 2) cycloaddition reaction, they afford functionalised 6H-1,3-thiazine 6-ones, the electrophilic properties of which are described. This cycloaddition gives rise to other reaction products resulting from the addition of two or three molecules of ketene according to the nature of the substituents.

Rearrangement of 1-O-(thio-p-nitrobenzoyl)thiocarbonyl galactoside: a novel access to α-thioglycoside derivatives

The synthesis of galactosides thiolate and thioester is described by direct S-glycosylation process from 1-O-(thio-p-nitrobenzoyl)thiocarbonyl galactoside. Three novel anomeric groups are presented as potent glycoside activators: O-(thio-p-nitrobenzoyl)thiocarbonyl, O-(imidazolyl)thiocarbonyl and S-thio-p-nitrobenzoyl.

SYNTHESIS OF THIAAZAHETEROCYCLE NUCLEOSIDE ANALOGUES

ABSTRACT The syntheses of thiazinone, thiazinedione and thiazolinone base modified nucleoside analogues have been discussed in both the deoxy- and ribosyl series. Both inter- and intramolecular N-glycosylations were evaluated.

Electrochemical access to functionalized dihydrothiopyran derivatives-Part 2. Electroreduction of triactivated 4H-thiopyrans

Electrochemical behaviour of triactivated thiopyrans has been investigated in protic medium. Electroreduction of 4-dimethylamino-2,3,5-trimethoxycarbonyl-4H-thiopyran I first led to 2,3, 5-trimethoxy-carbonyl-2H-thiopyran IV, with elimination of dimethylamine; further reduction at more negative potential gives equimolar mixture of 2,3,6-trimethoxycarbonyl-3,6-dihydro-2H-thiopyran V and 2,3, 6-trimethoxycarbonyl-5,6-dihydro-2H-thiopyran VI. The same mixture is obtained by reduction of either 4-dimethylamino-3,5,6-trimethoxycarbonyl-3,4-dihydro-2H-thiopyran II or 3,5,6-trimethoxycarbonyl-2H-thiopyran III. Intermediate formation of a delocalised carbanion is postulated in order to explain these results.

Reactivity of 1,1'-thiocarbonyldiimidazole with glycosides: a novel and efficient glycosidic activation

Abstract The synthesis of monoglycosyl imidazoles and 1,1′-di- O -glycosides is described by direct glycosylation process from reducing sugar in the presence of 1,1′-thiocarbonyldiimidazole. Novel anomeric groups as 1- O -(imidazolyl)thiocarbonyl and 1- O -(imidazolyl)carbonyl are presented as potent glycosidic activators.