CS274394B1 - Method of optically active 2-deoxy-l-ribose preparation - Google Patents

Abstract

The solution concerns a method of production of extremely pure optically active 2-deoxy-L-ribose. In 1,5 to 3 percent by weight of water solution mixture of lactones of 3-deoxy-L-gluconic acid and 3-deoxy-L-manonic acid, by means of electrolytic oxidation a glycosidic bond is split in acid environment during catalytic action of cerium ions at a current density of 1.5 to 3 A/dm<2> at a temperature of 35 to 55 degrees C for a period of 9 to 14 hours. The crystalline N-phenyl-2-deoxy-L-rybosilamine is prepared from the reaction mixture by means of aromatic amine and from this N-phenyl-2-deoxy-L-rybosilamine the 2-deoxy-L-ribose is released by hydrolysis by water vapour. Then it is cleaned in active carbon and crystallized from the methanol acetone mixture.

Description

The invention relates to a process for the preparation of optically active 2-deoxy-L-ribose.

2-Deoxy-L-ribose is a rare carbohydrate of deoxy-sugars with biological activity.

Most commonly, it is prepared by the glykalic method from L-arabinose via intermediates-s-ob-tet-O-acetyl-L-arabinose-α-acetobromo-1-arabinose -> - 3,4-diacetyl-1-arabinal -> - L-arabinal- > -2-deoxy-L-ribose / CS Hudson, J.A.Chem.Soc. 47

270 (1925), R.E. Deriaz, W.G. Overend, M. Stacey, Ehbel, G. Teece, L.E. Wiggins: J.Chem.

Soc. 1879 (1949)]. It can also be prepared by isolation from thymus nucleosides / P.A. Levine, A. Mikeskal, T. Sea: J.Biol.Chem. 85, 785 (1930); M. Gehrke, F.Y. Aichner: Ber. 60

918 (1927)].

It is known to prepare metasaccharin acids from D-glucose as well as to degrade them in the form of calcium salts with hydrogen peroxide in the presence of an iron salt to 2-deoxy-L-ribose / G.N. Richards: Methods in Carbohydr. Chem. Vol I. 180 (1963), J. Chem. 3638 (1954)].

The above methods of preparation of 2-deoxy-L-ribose had the drawbacks that the yield of the intermediates as well as the end product was low, the preparation was long and difficult. The final product did not achieve the desired purity.

The above-mentioned disadvantages are substantially eliminated by the process according to the invention for the preparation of 2-deoxy-L-ribose, which consists in reducing the lactones of 3-deoxy-L-gluconic acid in 1.5 to 3% aqueous solution. and 3-deoxy-L-manon electrolytic oxidation cleaves the glycosidic bond by acidifying a direct current in an acidic environment under the catalytic action of cerium ions, at an anode current density of 1.5 to 3 A / dm, at a temperature of 35 to 55 ° C for 9 to 55 ° C. 14 h, then crystalline N-phenyl-2-deoxy-L-ribozylamine is prepared from the reaction mixture after neutralization in the presence of ethanol in an acidic medium by means of an aromatic amine, preferably aniline, from which the 2-deoxy-L-ribose is liberated by water vapor hydrolysis , it is purified by activated carbon and deionized on ion exchangers of the cation exchange resin in the H ⁺ form and the anion exchange resin in the AC 'form and the methanol crystallizes acetone from the mixture.

The advantage of the proposed process for the preparation of 2-deoxy-L-ribose over the prior art methods is that the process is more economical, the utilization of the starting material is better, the technological operations are not equipment intensive and the final product achieves high purity.

The invention is illustrated by the following non-limiting example.

Example 1

To a 10 L glass reaction vessel equipped with stirring, cooling and two graphite electrodes (anode and cathode) was added a mixture of lactones of 3-deoxy-L-gluconic acid and 3-deoxy-L-manonic acid (225 g), sulfuric acid 0.1% wt. (7,500 mL), cerium sulfate monohydrate (56 g). From a unidirectional electric current source, the current intensity was adjusted so that the anode current density was 3 A / dm 2 at 50 ° C for 12 h with stirring. The reaction mixture was neutralized with calcium carbonate (150 g) and the salts were filtered off. The filtrate was concentrated to a volume (300 ml) at a pressure of 100 kPa and a temperature of 40 ° C, aniline (60 ml), 96 wt. ethanol (60 ml), acetic acid 98 wt. (2.4 mL). Stir at 5 ° C for 2 h. Gradually, N-phenyl-2-deoxy-L-ribozylamine began to crystallize. After 24 h, it was filtered, washed under suction with cold water (1500 ml) and the wet N-phenyl-2-deoxy-L-ribozylamine was stirred in water (3000 ml) and decomposed in a distillation apparatus with water vapor for 1 h. The solution was decolorized by the addition of activated carbon (50 g), filtered, and the filtrate desalinated by percolation on columns with a sulfonated functional ion exchanger in hydrogen form and a benzyltrimethylammonium functional quaternary ion exchanger in acetate form 30 cm long and 5 cm in diameter. The solution was concentrated to a syrup at 40 mbar and 40 ° C and lyophilized (97 g). The lyophilisate was dissolved 1: 1 methanol: acetone (190 mL) and crystallized at 5 ° C. 2-deoxy-L-ribose optical

CS 274394 B1 rotation / θ / βθ + 57 ^° (c = 2 water), mp 86-88 ° C was obtained in 48% yield.

2-Deoxy-L-ribose has utility in carbohydrate chemistry and biochemistry, genetic engineering, and medicine.

Claims (2)

Process for the preparation of 2-deoxy-L-ribose, characterized in that at 1.5 to 3.0 wt. of an aqueous solution of a mixture of 3-deoxy-L-manonic acid β-lactones by electrolytic oxidation cleaves the glycosidic bond in an acidic environment under the catalytic action of cerium ions at an anode current density of 1.5 to 3 A / dm @ 2 at 35 to 55 ° C. for 9 to 14 h, crystallized N-phenyl-2-deoxy-L-ribozylamine is prepared from the reaction mixture after neutralization in the presence of ethanol in an acidic medium by means of an aromatic amine, from which 2-deoxy-L-ribose is liberated by water vapor hydrolysis, It is purified by activated charcoal and the methanol is crystallized from acetone. 2. A process according to claim 1, characterized in that, after purification with activated charcoal, the cation exchangers are cationized in the H ^{@ +} form and anion exchanged in the Ac @ - form.