GUIDOE. HILBERT
330
VOl. 59
u. s. DEPARTMENT OF AGRICULTURE] Synthetic Nucleosides-Some 1-Glycosidouracils
[CONTRIBUTION FROM THE BUREAU OF CHEMISTRY AND SOILS,
BY GUIDOE. HILBERT Of the two known methods for synthesizing py- satisfactory. The products (11) were converted rimidine nucleosides, the one most recently intro- by simultaneous deacetylation and deethylation duced, involving the interaction of 2,4-dialkoxy- with alcoholic hydrogen chloride into the correpyrimidines and acetobromosugars, has the dis- sponding 1-glycosodouracils, which, like uridine, tinct advantage of actually introducing the sugar neither respond to the Wheeler-Johnson color test into the pyrimidine ring a t the 1-position, which nor reduce Fehling’s solution after acid treatment. is that occupied by ribose in uridine and cytidine. It is interesting that the pentose-pyranosidouraUnfortunately the method seemed not to be as cils melt considerably higher, are thermally more general as first expected. For example, two stable and are much less soluble in water than uriother types of pyrimidines, namely, 2-methoxy- dine and the hexose-pyranosidouracils. Evi4-amin0-~ and 2,4-dimethoxy-5-methyl-pyrimi-dently the presence of a carbinol side group on a dine3formed in the presence of acetobromoglucose sugar ring d e c t s significantly the properties of only methylated derivatives. These results sug- the nucleosides. gest that the success of the method is dependent Of the acetobromosugars investigated, acetoto a marked extent upon the nature of the sub- bromo-d-mannose, because of the similarity of its stituents attached to the pyrimidine cycle. The chemical reactions with those of acetobromo-dfollowing investigation was initiated (a) to test ribose (“orthoacetate” formation’), was considthe generality of the reaction between various ered to offer the most promise of producing an acetobromosugars and 2,4-diethoxypyrimidine analog of (I). Unfortunately, the interaction of and (b) with the hope of obtaining compounds acetobromo-d-mannose and 2,4-diethoxypyrimisimilar in constitution to the anomalous 4-ethoxy- dine gave a sirup and the lability of the desired 2-triacetyl-d-ribosidopyrimidine(I) obtained as product precluded fractionation of the sirup to a by-product in the interaction of acetobromo-d- remove by-products. In view of the sluggishness ribose and 2,4 - dieth~xypyrimidine.~If such a with which most mannose derivatives crystallize product could be formed from an easily accessible and the complexity of the reaction product, this sugar, there would be no difficulty in the way of result was not altogether unexpected. However, obtaining sufficient material for a proof of struc- presumptive evidence in favor of the formation of ture. an analog of (I) in this reaction was obtained in Four different sugar derivatives, namely, aceto- the following manner. When the sirup was albromo-d-galactose, acetobromo-d-xylose, aceto- lowed to stand for a considerable length of time, a bromo-l-arabinose and acetobromo-d-mannose, crystalline material gradually deposited. After were used in this work. Each of the first three gave separation and purification i t proved to be 1,2which had with 2,4-diethoxypyrimidine compounds of the dihydro-2-keto-4-ethoxypyrimidine16 type (11); in none of these reactions could crystal- been obtained previously from the mild alkaline hydrolysis of (I), Presumably this was formed by 0 II the slow hydrolysis of 4-ethoxy-2-tetraacetyl-dC-N mannosidopyrimidine. Since the formation of a (11) Acetyl sugar -N )\COC& pyrimidine substituted in the 1-position by manc=c H H nose was of less immediate interest, no effort was line analogs of the labile 4-ethoxy-2-triacetyl-d- made to prepare 1-d-mannosidouracil by using a ribosidopyrimidine (I) be isolated. Considering procedure similar to that employed for the isolathe number of side reactions that are possible (see tion of 1-d-ribosid~uracil.~ below), the yields of the 1,2-dihydro-2-keto-4-eth- The 1,2-dihydro-2-keto-4-ethoxy-l-acetylglyoxy-1-acetylglycosidopyrimidines(11) are quite cosidopyrimidines (11) represented only a minor fraction of the product formed by the interaction (1) Hilbert and Johnson, THIS J O U R N A L , 62, 4489 (1930).
