CS275890B6 - Process for preparing l-ribose - Google Patents

Abstract

The method of preparing L-ribose is solved by cutting purity. 15-25% aqueous L-arabinose solution is contacted with a functional ion exchange resin quaternary benzyltrimethylammonium molybdenum-linked groups ions at 90 to 100 ° C for 4 to 4 hours 6 h. From the reaction mixture of L-ribose, L-arabinose, L-xyloxy, L-xyloyl is aromatic the amine produces crystalline N-phenyl-L-ribozylamine, from which water vapor hydrolysis release L-ribose. After removal of L-ribose sa mixture of sugars in mother liquor chromatographically selectively split on an ion exchange column functional sulfo groups which have been modified one, two or three valent metal 40-60% aqueous solution ethanol

Description

The invention relates to a process for the preparation of L-ribose.

L-ribose finds use not only in the synthesis of higher biologically active carbohydrates but also in medical practice. Due to its practical use, increased attention is paid to the preparation of L-ribose ’.

L-Ribose has heretofore been prepared from L-arabinose via intermediates 2,3,4-tri-o-acetyl-Uarabinosyl bromide-> 3,4-di-o-acetyl-L-arabinol— »L-arabinol (WCAustin, FL Humoller: J. Am. Chem. Soc., 56, 1152 (1952), 66, 1152 (1964); FLHumoller: Methods in Carbohydrate Chemistry Vol. V.Bilik,. J. Čaplovič prepared L-ribose from a mixture of L-arabinose, L-ribose in a ratio of 2: 1 by chromatography on cation exchange in barium form (Czech author's certificate 149472).

Said methods for the preparation of L-ribose had the disadvantages that the yield of synthesis intermediates was low, there was contamination of the environment, equipment for production and removal of pollutants was expensive and the final products did not reach the required purity.

These disadvantages are substantially eliminated by the method of preparation of L-ribose according to the invention by using L-arabinose as a starting material, which is produced from waste beet cuttings (V. Libeňský č. It is known that when an aqueous solution of L-arabinose is subjected to heating in the presence of molybdate ions, epimerization to L-ribose occurs (V. Silik: Chem. Zvěsti 26, 372 (1972); ELClark Jr., MLHayes, R. Barker : Carbohydr. Res., 153, 263 (1986)). In this case, L-xylose and L-lyxose also occur. As a result, it is very difficult to separate pure L-ribose from this mixture. Adjustment of the reaction conditions resulted in a reduction in the yield of the final product. The present inventors investigated the possibility of transforming an aqueous solution of L-arabinose to which it was treated with molybdate ions under heat and came to this invention by finding better recovery of the starting material and separation of L-ribose from the reaction mixture by a combined method using aromatic amine as well as aromatic amine. using an ion exchanger that has been cycled with a metal. They have found that crystalline N-phenyl-L-ribozylamine is preferentially formed and that the pentose mixture gives sharp elution zones which indicate a complete separation between them. _

The present invention substantially obviates the above disadvantages of preparing L-ribose in that a 15 to 25% aqueous solution of L-arabinose, preferably a 20% solution, is contacted with an ion exchanger with benzyltrimethyl ammonium functional quaternary groups which is modified with molybdate ions. at a temperature of 90 to 100 ° C, preferably 95 ° C for 4 to 6 h, preferably 5 h. From the resulting mixture of L-ribose, L-arabinose, L-lyxose, L-xylose using an aromatic amine, preferably aniline, a crystalline N-phenyl-L-ribozylamine is prepared, from which L-ribose is released by steam hydrolysis. Hydrolysis of N-phenyl-L-ribozylamine with steam has the advantage that no incrustations are formed, no further operations such as neutralization, washing, concentration as in acid hydrolysis are required, which is reflected in the higher yield and quality of the final product. The parent drug, which contains L-ribose, L-arabinose, L-lyxose, L-xylose, is chromatographically selectively separated on a column with a sulphon-functional ion exchanger which has been modified with a mono-, di- or trivalent metal, preferably silver, using 40 to 60% aqueous ethanol solution, preferably 50% aqueous ethanol solution.

The proposed method of preparation of L-ribose is more efficient and economical than the previous method of preparation. The device is affordable, technological operations are simpler, less energy-intensive. Unreacted starting L-arabinose can be used in its entirety for the next reaction as well as an ion exchanger after simple activation. This substantially increases the yield of L-ribose and, at the same time, other crystalline rare carbohydrates L-lyxose and L-xylose of high purity are obtained.

Example 1

L-Arabinose (10 kg) was dissolved in water (40 L), added with tert-benzyltrimethyl ammonium groups attached, and stirred in a reactor at 95 ° C for 5 h. The reaction exchanger with functional quarmolybdate ions (1 kg) is separated from the mixture by filtration from

CS 275890 B 6 2 ion exchanger, decolorized by the addition of activated carbon (0.2 kg) and concentrated to an evaporator at a pressure of 100 kPa and a temperature of 40 ° C to a syrup (11.8 kg) and crystallized from ethanol (35.5 L). Crystallized L-arabinose (5.8 kg) was returned to the reaction and the above procedure was followed. This reaction is repeated a total of 3 times. After crystallization of L-arabinose, the solutions are desalted on a benzyltrimethylammonium quaternary functional ion exchanger in acetate form on a column 200 cm long and 10 cm in diameter so that the desalted solution does not exceed a conductivity of 70 / US and concentrated to a syrup (9 kg).

To a mixture of L-ribose, L-arabinose, L-lyxose, L-xylose (9 kg) was added water (29 L), aniline (4.7 L), ethanol (8.6 L), acetic acid (0 L, 02 1). Stir at 5 ° C for 1 h. N-phenyl-L-ribozylamine gradually begins to crystallize. After 24 h, it is filtered off with suction and washed with water (50 L).

Wet N-phenyl-L-ribozylamine (26 kg) was stirred in water (150 L) and decomposed in a steam distiller for 1 h. The solution is decolorized, decolorized by the addition of activated carbon (0.4 kg) and the filtrate is desalted on columns with a sulfo-functional ion exchanger in hydrogen form and a quaternary benzyltrimethylammonium-functional ion exchanger in acetate form with a length of 200 cm and a diameter of 10 cm. The solution is concentrated on an evaporator at a pressure of 100 kPa and a temperature of 40 ° C to a syrup and lyophilized (7.2 kg). The lyophilisate was dissolved in ethanol (14.5 L) and L-ribose (3.7 kg) crystallized. Recrystallization gave additional L-ribose (1.7 kg). L-Ribose had an optical rotation (cC) + 20 ° (c = 2 water), m.p. 83 ° C.

The solution, after removal of N-phenyl-L-ribozylamine (50 L), is decomposed in a distillation apparatus with steam for 1 h. After removal of the aniline, the solution is purified as described above. A mixture of L-ribose, L-arabinose, L-lyxose, L-xylose (0.8 kg) was dissolved in 50% aqueous ethanol (0.8 L) and applied to a column packed with a sulfo-functional ion exchanger in silver form (Dowex 50 WX 8 with a grain size of 0.07 to 0.13 mm) and a column length of 2 m and a diameter of 0.12 m. A 50¾ aqueous ethanol solution is used as eluent. Using a fraction collector at a flow rate of 40 ml. h ¹ , the individual fractions are analyzed spectromotometrically at 3,55 nm with 3,5-dinitrosalicylic acid as well as by ascending paper chromatography. (Whatman No 1) in an ethyl acetate: pyridine: water system in a volume ratio of 8: 2: 1 and detected with alkaline silver nitrate.

Fraction 1 contained L-xylose (140 g), fraction 2 contained L-lyxose (75 g), fraction 3 contained L-arabinose (238 g), fraction 4 contained L-ribose (215 g). The fractions were individually concentrated on an evaporator at a pressure of 100 kPa and a temperature of 40 ° C to a syrup, purified by adding activated carbon (50 g) and crystallized from ethanol.

L-Xylose had an optical rotation of 20 ° (c = 2 water), a melting point of 149 ° C and was obtained in 21% yield.

L-Lyxose had an optical rotation of ⁺ 13 ° (c = 2 water), a melting point of 104 ° C and was obtained in 11% yield.

L-Arabinose had an optical rotation of I <6 + 1.04 ° (c = 2 water), a melting point of 163 ° C and was obtained in 36% yield. . ,

L-Ribose had an optical rotation / οί / θθ + 20 ° (c = 2 water), a melting point of 82 ° C and was obtained in 32 ¾ yield.

L-Ribose has applications in chemistry, carbohydrate biochemistry, genetic engineering and medicine.

Claims (5)

PATENT CLAIMS A process for the preparation of L-ribose, characterized in that a 15 to 25¾ aqueous solution of L-arabinose is contacted with an ion exchanger with functional quaternary benzyltrimethylammonium groups with bound molybdate ions at a temperature of 90 to 100 ° C for 4 to 6 hours. a mixture of L-ribose, L-arabinose, L-lyxose, L-xylose is contacted with an aromatic amine to form crystalline N-phenyl-L-ribozylamine, from which L-ribose is released by steam hydrolysis. 2. A process according to claim 1, characterized in that a 20¾ aqueous solution of L-arabinose is contacted with an ion-ionizer with functional quaternary benzyltrimethylammonium groups with bound molybdate ions at a temperature of 95 ° C for 5 hours. 3. The process of claim 1, wherein the aromatic amine is aniline. 4. The process according to item 1, characterized in that the mother liquor containing L-ribose, L-arabinose, L-lyxose, L-xylose is chromatographically selectively separated on a column with a sulfo-functional ion exchanger which has been modified one, bivalent or trivalent metal using a 40 to 60 ¾ aqueous ethanol solution. . 5. The process according to item 4, characterized in that the selective chromatographic separation is carried out in silver form using a 50¾ aqueous ethanol solution.