DD250126A1 - PROCESS FOR THE PRODUCTION OF URONSAFE DERIVATIVES - Google Patents

Abstract

The invention relates to a process for the preparation of acetylated (6-deoxy-D-heptopyranoside) uronimidesaeure- or thioimidsÄure alkyl ester hydrochlorides. The aim of the invention is to develop a process for the preparation of these uronic acid derivatives. The uronic acid derivatives of the general formula III in which R is an alkyl radical, R 1, R 2 is a hydrogen atom or an acetoxy group, R 3 is an alkyl radical and X is an oxygen or sulfur atom, can be prepared by reacting the nitriles of the general formula I, in R, R 1 and R 2 have the abovementioned meaning, with alcohols or thioalcohols of the general formula II in which R 3 and X are as defined above, in the presence of hydrogen chloride. These uronic acid derivatives can be used as organic intermediates for further syntheses. They are particularly suitable for the preparation of C-nucleoside analogs having potentially biologically active properties.

Description

For this 1 page formulas

Field of application of the invention

The invention relates to a process for the preparation of acetylated (e-deoxy-D-heptopyranosidluronimidic acid or thioimidic acid alkyl ester hydrochlorides.

These uronic acid derivatives can be used as organic intermediates for further syntheses. They are particularly suitable for the preparation of C-nucleoside analogs having potentially biologically active properties.

Characteristic of the known technical solutions

Acetylated (6-deoxy-D-heptopyranoside) uronimidic acid or thioimidic acid alkyl ester hydrochlorides are not yet known.

Object of the invention

The aim of the invention is to develop a process for the preparation of these uronic acid derivatives.

Explanation of the essence of the invention

The uronic acid derivatives of the general formula III in which R is an alkyl radical, R ¹ , R ^{2 is} a hydrogen atom or an acetoxy group, R ^{3 is} an alkyl radical and X is an oxygen or sulfur atom, can be prepared by reacting the nitriles of the general formula I in which R, R ¹ and R ^{2 have} the abovementioned meaning, with alcohols or thioalcohols of the general formula II, in which R ³ and X are as defined above, in the presence of hydrogen chloride. The reactions are carried out in an absolute aprotic solvent, preferably in diethyl ether. It is expedient to react the nitriles I and the alcohols or thioalcohols II in a molar ratio of 1: 1. An excess of hydrogen chloride should be used. The reaction temperatures are around 0 ^° C. The reaction times are a few days. The procedure is as follows: The nitriles I are suspended in absolute diethyl ether. After addition of the alcohols or thio alcohols II is introduced into this suspension at ^{0 0} C dry hydrogen chloride to saturation. The uronic acid derivatives crystallize out of the reaction mixtures in quite pure form.

embodiments Embodiment 1

(Methyl) - tri-O-acetyl-e-deoxy-aD-gluco-heptopyranosidyluronimic acid ethyl ester hydrochloride 0.01 mol methyl-2,3,4-tri-O-acetyl-6-cyano-6 deoxy-D-gluco-pyranosidwird suspended in 20 ml of absolute ether. one adds 0.01 mol absolute ethanol and forwards in said suspension at ⁰ ° C until saturation, a dry hydrogen chloride. The resulting solution is 3 days at 5 ⁰ C The reaction mixture is concentrated in vacuo, the residual crystalline precipitate is washed with absolute ether, and it is dried over phosphorus pentoxide in a desiccator, yield: 70% of theory, melting point: 118-120 ° C.

[α] ² , ¹ = + 18.92 ° (c = 1, DMSO) C ₁₆ H ₂₆ CINO ₉ (411.8) Ber. C46.66 H 6.36 N 3.40 Gef. C 46.37 H 6.60 N 3.70

Embodiment 2

(Methyl 2,3,3-tri-O-acetyl-6-deoxy-aD-gluco-heptopyranoside) -uronothioimidic acid benzyl ester hydrochloride 0.01 mole methyl-2,3,4-tri-0-acetyl-6 -cyano-6-deoxy-aD-glucopyranoside and 0.01 mol of benzyl mercaptan are reacted in 50 ml of ether, as described in Example 1. Yield: 92% of theory. Melting point: 50-70 ⁰ C

[a] g ¹ = + 20.98 ° (c = 1, DMSO)

C ₂₁ H ₂₈ CINO ₈ S (489.9) Ber. C51.48 H 5.76 N2.86 S6.54 Gef. C51.17 H 6.10 N 2.91 S 6.64

R ²

CH ₂ CN

R ³ XH / HCl

R ¹ ,

XR ³ .HCl I CH ^ C = NH

R _

hl

OR

Claims (2)

A process for the preparation of uronic acid derivatives of general formula III in which R is an alkyl radical, R ¹ , R ^{2 is} a hydrogen atom or an acetoxy group, R ^{3 is} an alkyl radical and X is an oxygen or sulfur atom, characterized by that nitriles of the general formula I, in which R, R ¹ and R ^{2 have} the above meaning, are reacted with alcohols or thioalcohols of the general formula II in which R ³ and X are as defined above, in the presence of hydrogen chloride. 2. The method according to item 1, characterized in that an excess of hydrogen chloride is used.