976. The synthesis of 9-glycitylpurines, 3-glycityl-[1,2,3]-triazolo[d]-pyrimidines, 8-glycitylpteridines, and 10-glycitylbenzo[g]pteridines, including riboflavin and riboflavin 2-imine

Abstract

Davoll and Evans. 5041 Y'he Synthesis of 9-Glycitylpu~ines, 3-GZycityl-[ 1,2,3]-triaxolo[d]pyrimidines, 8-Glycitylpteridines, and lO-C7'lycitylbe.~~zo[g]pteridines,including Riboflavin and Riboflavin 2-lmine.By J. DAVOLL and D. D. EVANS.5-Aniino-4-glycitylaminopyi-imidines, prepared froin appropriate &nitroor 5-nitroso-derivatives, have been converted by ring closure into the compounds named in the title.THE structural similarity between purine nucleosides, pteridines, and riboflavin has been noted by several authors,l. who have also suggested that 8-glycosyl-or S-glycitylpteridines may be involved as biosyiithetic intermediates. Recent work has shown that adenine and guanine can serve as precursors of the pyrimidine portion of riboflavin, and that 8-D-ribitylpteridines are also involved in its biosynthesis. The aim of the present work was the preparation of compounds which might be intermediates in these biosynthetic reactions or might act as antimetabolites to the compounds actually involved.Since all the required compounds (1-111) contain the carbon-nitrogen skeleton of a 5-amino-4-glycitylaminopyrimidine as part of their structures, the preparation of this class of compound was investigated. Suitable precursors were readily obtained from appropriate chloropyrimidines and glycitylamines in boiling aqueous or aqueous-ethanolic solution ; thus, 6-amino-4-chloro-5-nitropyrimidine and D-ribitylamine (2 mols.) gave 6-amino-5-nitro-4-~-ribitylaminopyrimidiiie (83% yield), which on catalytic hydrogenation afforded the triamine (Ia) ; the sorbitylamino-compound (Ib) was similarly prepared by starting from u-glucitylamine. N HOf' )NHR a : K = u-ribityl. b : R = D-sorbityl.4-Alkylarnino-2,5-diamino-6-hydroxypyrimidines (I1 ; R = alkyl) have been prepared by heating 2-amino-4-chloro-6-lljrdroxypyrimidine with an excess of alkylamines at 120-140" and then introducing a 5-amino-group by nitrosation or by azo-coupling l1 followed by reduction. Alternatively, 2-amino-4-chloro-6-hydroxy-5-pheiiylazopyrimidine

Synthesis of Certain 6-(Arylthio)uracils and Related Derivatives as Potential Antiviral Agents

“…6-Chlorouracil 3, the key starting material necessary for this study, was synthesized from barbituric acid 1 via reaction with phosphorus oxychloride and dimethylaniline to yield 2,4,6-trichloropyrimidine 2, 29 which was subsequently hydrolysed with aqueous sodium hydroxide 30 to yield 3. Interaction of 6-chlorouracil 3 with benzyl chloride or 4-chlorobenzyl chloride in dimethylsulphoxide, in the presence of potassium carbonate yielded the corresponding N 1 -substituted derivatives 4a 31 and 4b.…”

Exploring the Mechnisms of Molecular Recognition by Flavins

“…The different synthetic routes for flavins involve the condensation of 2-arylazo compound with barbituric acid [74 ± 77], aniline with violuric acid [78] and 4-halouracil [79], quinoxaline with guanidine [80] [81], and ortho-benzoquinone with diaminopyrimidine [82]. The acid-catalyzed cyclocondensation of 2-(substituted amino)aniline (4) with alloxane monohydrate (5) is an important and most-often used method to synthesize flavins 6 (Scheme 1) [83 ± 94].…”

Polychloroheteroaromatic Compounds

“…6-Chlorouracil is obtained when the 2,4,6-trichloro-compound is hydrolyzed with hot aqueous sodium hydroxide [586,603]. 6-Chlorouracil is probably best prepared, however, by hydrolysis of 6-chloro-2,4-dimethoxypyrimidine (preceding paragraph) with dilute mineral acid [604].…”