Jose L. Jimenez Requejo

Facile preparation of C-glycosylbarbiturates and C-glycosylbarbituric acids

Abstract A general method for the synthesis of pyrimidine C -nucleosides involves a one-step reaction of aldohexoses and aldopentoses with barbituric acids. Thus, 2-amino-2-deoxy- d -glucose was converted into 5-(2-amino-2-deoxy-β- d -glucopyranosyl)barbituric and 5-(2-amino-2-deoxy-β- d -glucopyranosyl)-1,3-dimethyl-barbituric acids. Likewise, d -glucose, d -galactose, d -mannose, d -xylose, d -ribose, and d -arabinose were transformed into sodium 5- d -glycopyranosyl-1,3-dimethyl-barbiturates ( 11–16 ; average yields of 80%). The free acids 17 and 18 , with the α- d -arabinopyranosyl and β- d -galactopyranosyl structures, were also obtained. Acetylation of 11–18 gave O -acetylated 1,3-dimethyl-2,4,6-trioxo-1 H ,3 H ,5 H -pyrimidin-5-ylidene-alditols, although some compounds with pyranoid structures were also obtained.

Synthesis of 1,3,4,6-tetra-O-acetyl-2-[3-alkyl-(aryl)-thioreido]-2-deoxy-α-d-glucopyranoses and their transformation into 2-alkyl(aryl)amino-(1,2-dideoxy-α-d-glucopyrano)[2,1-d]-2-thiazolines

Abstract 1,3,4,6-Tetra- O -acetyl-2-deoxy-2-isothiocyanato-α- d -glucopyranose, produced from 1,3,4,6-tetra- O -acetyl-2-amino-2-deoxy-α- d -glucopyranose hydrochloride, thiophosgene, and calcium carbonate, was condensed with alkyl- and aryl-amines in ether to afford the crystalline 1,3,4,6-tetra- O -acetyl-2-[3-alkyl(aryl)-thioureido]-2-deoxy-α- d -glucopyranoses ( 2 ). Compounds 2 and the β anomers 3 were converted in high yield into 2-alkyl(aryl)amino-(3,4,6-tri- O -acetyl-1,2-dideoxy-α- d -glucopyrano)[2,1- d ]-2-thiazoline hydrobromides ( 4 ) by hydrogen bromide-promoted cyclisation. The O -deacetylated thiazoline hydrobromide 5 was also isolated and converted into 2-[ N -(4-methoxyphenyl)acetamido]-(3,4,6-tri- O -acetyl-1,2-dideoxy-α- d -glucopyrano)[2,1- d ]-2-thiazoline ( 8 ). Conformational studies of 4 and 8 were made by 1 H-n.m.r. spectroscopy.

Preparation of C-nucleosides by dehydration of pentahydroxypentyl-heterocycles: Steric course and mechanism

Abstract The acid-catalysed dehydration of pentahydroxypentyl-heterocycles can take place between C-1′ and C-4′ to yield C -nucleosides having furanoid structures, or between C-1′ and C-5′ to yield pyranoid compounds. Each reaction can yield one of the two possible anomers or a mixture of both. We have dehydrated pentahydroxypentyl-heterocycles having d - gluco , d - manno , and d - galacto configurations. When the reactions were kinetically controlled, the 6,6-dimethyl-2-(pentitol-1-yl)-4,5,6,7-tetrahydroindol-4-ones having the d - gluco or d - manno configurations yielded 2-α- d -arabinofuranosyl-6,6-dimethyl-4,5,6,7-tetrahydroindol-4-one, but they yielded 2-α- d -arabinopyranosyl-6,6-dimethyl-4,5,6,7-tetrahydroindol-4-one under conditions of thermodynamic control. Dehydration of 3-acetyl-2-methyl-5-( d - galacto -pentitol-1-yl)-1-propylpyrrole gave a mixture of 3-acetyl-5-(α- and β- d -lyxopyranosyl)-2-methyl-1-propylpyrrole. These results are consistent with a mechanism involving an intermediate C-1′ carbocation.

Acylation of glycofurano[2,1-d]imidazolidine-2-thiones: A structural revision

Abstract Acetylation of glycofurano[2,1- d ]imidazolidine-2-thiones leads to the O -acetylated or N -acetylated, O -acetylated glycofurano[2,1- d ]imidazolidine-2-thiones depending on the reaction conditions. The position of acetylation on the imidazolidine-2-thione ring was demonstrated by spectroscopic data and by transformation of CSaCO groups. The formation of a glycofuranoimidazolidine-2-thione by the reaction of a 2-amino-2-deoxyaldose with potassium thiocyanate has not been observed hitherto.

1-Aryl(glycofurano)imidazolidine-2-thiones derived from new 2-(alkylamino)-2-deoxyheptoses having d-glycero- d-galacto and d-glycero-d-talo configurations

Abstract The aminonitrile synthesis applied to d -mannose gave, in good yield, a mixture of the two epimeric heptosamines 2-deoxy-2-(ethylamino)- d -glycero-α- d -galacto-heptopyranose and 2-deoxy-2-(ethylamino)- d -glycero-β- d -talo-heptopyranose that could be fractionated by recrystallization. The stereochemistry at C-2 of both amino sugars, and of their acyl derivatives, was established from their 1H-n.m.r. spectra. This stereochemistry was also demonstrated by the preparation of the 3-alkyl-1-aryl(glycofurano)imidazolidine-2-thiones, whose structures were assigned from the 1H-n.m.r. spectra of their tetra-O-acetyl-derivatives. In a similar way, hemihydrogenation of the epimeric mixture of 2-deoxy-2-(propylamino)-heptononitriles gave an amorphous mixture of 2-deoxy-2-(propylamino)heptoses having the d -glycero- d -galacto and d -glycero- d -talo configurations. By reaction of this mixture with phenyl isothiocyanate, 1-phenyl-3-propyl-(1,2-dideoxy- d -glycero-β- d -talo-heptofurano)[2,1-d]imidazolidine-2-thione (21) was obtained. The structure of 21 was also demonstrated from the 1H-n.m.r. spectrum of its acetyl derivative.

Synthesis of glycofurano[2,1-d]imidazolidin-2-ones

Abstract Several 2-(3-arylureido)-2-deoxyglycopyranoses ( 13–16 ) have been converted into the corresponding 1-aryl-(1,2-dideoxyglycofurano)[2,1- d ]imidazolidin-2-ones ( 17–20 ) by acid-catalyzed cyclization. Acetylation of these compounds gave 1-aryl-(per- O -acetyl-1,2-dideoxyglycofurano)[2,1- d ]imidazolidin-2-ones ( 21–24 ) or 3-acetyl-1-aryl-(per- O -acetyl-1,2-dideoxyglycofurano)[1,2- d ]imidazolidin-2-ones ( 25–28 ) depending on the reaction. 3-Ethyl-1-phenyl-(1,2-dideoxy- d - glycero -β- d - talo -heptofurano)[2,1- d ]imidazolidin-2-one ( 33 ) was obtained by the reaction of 2-deoxy-2-ethylamino- d - glycero -β- d - talo -heptopyranose with phenyl isocyanate, and converted into the tetra-acetate 34 .

Synthesis of 1-aryl-(glycofurano)imidazolidine-2-thiones from new 2-(alkylamino)-2-deoxyhexoses

Abstract The new amino sugars 2-deoxy-2-(ethylamino)-α- l -glucopyranose, 2-deoxy-2-(propylamino)-α- l -glucopyranose, and 2-deoxy-2-(ethylamino)-α(or β)- l -mannopyranose have been prepared from l -arabinose by the aminonitrile synthesis. The reaction between these aminohexoses and aryl isothiocyanates affords the corresponding 3-alkyl-1-aryl-(1,2-dideoxy-α- l -glucofurano)[2,1- d ]imidazolidine-2-thiones and 3-alkyl-1-aryl-(1,2-dideoxy-β- l -mannofurano)[2,1- d ]imidazolidine-2-thiones. The structures of the new compounds described were elucidated by chemical and physical methods.