SU456808A1 - The method of obtaining 1-arabinofuranosylcytosine - Google Patents

Description

(54) METHOD FOR OBTAINING bp-D-ARABINO-URANOSYL CYTOSINE

the precipitate is dissolved in 100 ml of methanol, filtered through activated carbon, after which the solvent is evaporated in vacuo. The residue is then chromatographed on a silica gel column and the fraction containing arabinofuranosylcytosine is collected and evaporated in vacuo. 650 mg (59%) of substance are obtained which is chromatographically and electrophoretically identical to the sample. Some of this substance is treated with hydrogen chloride (conversion). To a solution of 159 mg (0.66 mmol) of l-p-D-arabinofuranosylcytosine in 1.6 ml of water was added 0.35 ml of 2N. HC1.

The cloudy solution is diluted with 3 ml of water, filtered and evaporated in vacuo. The residue is then re-distilled with ethanol, and then crystallized from 2 ml of methanol. By crystallization, 81 mg of l-p-D-arabinofuranosylcytosine hydrochloride are obtained, m.p. which is 196-198 ° C and which is chromatographically and electrophoretically identical to the sample. Evaporation of the mother liquors and subsequent crystallization gives 40 mg of a substance with the same properties.

Otic properties (rotational ability) -f 135.6 ° C (s 0.337, water). Ultraviolet spectrum: A maximum of 213 and 281 nm (loge 4.19 and 4.33), I am at least 242 nm (loge 3.31) (0.01 n. PS1), I am maximum 214 and 272 nm (loge 4.03 and 3.99), I am at least 250 nm (loge 3.77) (0.01 n. NaOH).

Calculated,%: C 38.68; P 5.05; N 15.05; C1 12.68.

CsHisHsOsHCl.

Found,%: C 38.41; H 4.83; N 14.89; C1 12.92.

Mol weight 297.7.

Example 2. To a dimethylformamide in an amount of 10 ml was added 1.01 g of cytidine, 1.52 g of diphenyl carbonate and 0.18 ml of water. The reaction mixture is then heated for 1 hour in a bath heated to 140 ° C. After cooling, the reaction mixture is poured into 100 ml of ether.

whereupon the precipitate formed is separated from the ethereal solution and then dissolved in 100 ml of methanol. After filtering over activated carbon, the solution is placed in a refrigerator for 10-12 hours at + 3 ° C, after which the supernatant (floating layer from the top) is separated by filtering a small amount of the separated substance. The filtrate is evaporated in vacuo, and the residue is chromatographed on silica gel (silica gel). The fraction containing arabinofuranosylcytosine is evaporated in vacuo, and the residue is dissolved in 60 ml of methanol. 1.5 ml of 2 N is added to the solution. HC1, and the resulting product is then evaporated in vacuo. The residue is again distilled with ethanol in vacuo and dried, and then crystallized from 6 ml of methanol. 390 mg of hydrochloric 1-; p-O-arabinofuranosylcytosine are obtained, m.p. which is 196-198 ° C and which is both chromatographic and electrophoretic identical to the sample. By evaporation of the mother liquors and subsequent crystallization, 260 mg of the same substance are obtained. The total yield is 650 mg (64%).

The manufacturing processes described above are equally suitable for both the L series and the nucleoside series discussed.

Subject invention

Claims (2)

1. A method of producing lpD-arabinofuranosylcytosine, characterized in that, in order to increase product yield and simplify the process, cytidine is reacted with an organic reagent capable of isolating 2,3-cyclic carbonate or thiocarbonate, for example an active carbonate such as diphenyl carbonate, at 50-170 ° C in an organic solvent medium or in an aqueous medium, followed by isolation of the target product in pure form or as a salt. 2. A method according to claim 1, wherein the reaction with cytidine is carried out in the presence of an alkaline salt or water.