SU1160720A1 - Method of obtaining immobilizing periodates for selectiveoxidation of ribozides - Google Patents

Abstract

1. Immobilized periodates of the general formula. - (; -CHH &{;i-nd;:. CH-CHg CH-} 1 OHZ) CCH3SOO -fcH-CH HO CH -NlCHjyO with in: n: K: B ratio of 35; 6: 35 :: .24 5p 9.7: 10: 48.3: 32 for the selective oxidation of ribosides. 2. The method of obtaining immobilized. Shrydatov, concluded in TOM), that. an aqueous solution of iodine acid is mixed with acetic acid with (I sew a strongly basic anion exchange resin and a chloromethyl and aminated trimesh mine of styrene copolymer with 6-10% divnabnd benzene with a ratio of 10 ions and CB equal to 1: 1-5, at temperatures from -1 to +20 C and 1HF f, 5-3.0., And the invention relates to compounds of the general formula (I) -Gen-sdCh-ncn, DL Iijfn LIij / i CHj-I (CHjJjlO where m: n: K: B 35: 6: 35: 24 9, 7: 10: 48 3:32, which can be used when

Description

selective oxidation of rybozid, including in the synthesis of compounds, has antitumor activity, and the way they are prepared. e

Sodium metaperiodate (NalO) has received the greatest distribution in the oxidation of nucleosides in the literature; CU is used less frequently.

The NalOj used as the oxidation of tO bodies does not show selectivity, it is non-specific and simultaneously oxidizes ribosides, glucosides and galactosides. ,

The chain of the invention is the creation of oxide-15s for the selective oxidation of ribozides from the group of periodates.

Immobilized periodates of the general formula 1 are proposed for the selective oxidation of ribozides. 20

A method is also proposed for the preparation of immobilized periodates of formula I, which consists in mixing an aqueous solution of iodic acid with acetic acid salt of 25 basicity anion exchanger — porphylatized and aminated with trimethylamine copolymer of etirol with 6-10% divinylbenzene and matching. The scientific research institute of ions 104 and CHjCOO, equal to DZ 1: 1-5, at (-1) - (h-10) C and pH 1 ,.

The proposed method provides for obtaining selective peroDats with a yield of 90-99%. The method is simple, since the reaction takes place at atmospheric pressure, e sphere pressure, temperature (-1) (+20) and does not require special equipment. The immobilized periodates obtained during stau are more selective than sodium metaperiodate .40

They selectively oxidize ribosides in the presence of lucosides and galactosides, act mildly, oxidation occurs at a pH of 2.3-2.8 under conditions that preclude the possibility of the removal of 45 aglycones; The isolation of the oxidation products is simplified, the yield is clear. At the end of the oxidation process, the spent anion exchangers are easily separated from the reaction products by filtration, the acetic acid and iodic acid are regenerated by known methods.

In order to obtain periodates according to the presumed, method, strongly basic anion exchangers, obtained on the basis of gelins or macroporous cross-linked copolymers and divinyl benzal, in OH form; I mixed at room temperature with a 20% solution of acetic acid

acids, washed with water until the neutral reaction of the wash water, the suspension is stirred at (0) - (+ 5) C with 5 10% solution of iodic acid, filtered, rinsed on the filter with water (from 0 to 20 ° C) to neutral wash water. The obtained periodates are stored at (-4) - (- 20) C under such conditions the periodates are stable for a year. At 20-25 ° C, they are inactivated within 3-5 hours, while the anion 107 is reduced to 10J. Quantitative determination of oxidation products is carried out spectrophotometrically.

The content of divinylbenzene (DVB) in the copolymer and the granulation of ion exchangers are taken into account in accordance with the purpose of the obtained immobilized periodates.

The molecular permeability of anion exchangers of a continuous-gel-structure is inversely proportional to the amount of HBV in the copolymer. The smaller the diameter of the JMO molecules, which are supposed to be oxidized, the greater the content of TWO is permissible in immobilized periodates. ..; .

The choice of anion exchangers with a DVI content of 6–10%, granulation of 20–400 mesh in the proposed periodates is determined by their optimal molecular permeability for compounds with a molecular mass of 100–400 daltons (nucleosides). Anionites with DVB content of 12–16% have reduced molecular permeability and exchange capacity.

Anion CHjCOO present in

compounds in certain ratios, forms a redox-reducing pair jCOO and i buffer system with PH 1, ..., 0, creating favorable conditions for the selective oxidation of ribozides and the subsequent complete separation of chromatographically pure dialdehydes. Determination of the output of periodates.

Since several parameters of the carrier (humidity, specific gravity, acetic acid content) simultaneously change as a result of immobilization of iodic acid, the yield of the target product (S) is determined by the difference of the amounts of iodic acid introduced into the recycling (Q) and the returned, non-aligned iodic acid (G ). S Q-G

Molecular Weight HIO4ЗН О 228

Exchange capacity of anion exchanger Dowex OH 1.7 mg-eq / g.

The number of original anion exchange resin Dowex 1 OH 60,

Q 11.61 g, G 1.11 g, S 10.5 (example 1).

Example 1. 60 tons of Dowex 1 OH anion exchanger (DVB 6%, exchange capacity 1.7 mEq / g} humidity 43.3%) are mixed with 100 ml of 20% acetic acid for 30 minutes at room temperature, filtered, washed cold water on the filter to neutral reaction with washed water, cooled to -2 ° C, add a cooled) solution of 11, 6 g of iodic acid in 80 ml of distilled water and mix up to a pH of 1.5, filter in the cold (from 0 to 2C), rinse with cold water until neutral wash water, the combined filtrate is evaporated, return 1.1 g of iodine dihydrate oh acid. A glass filter gives a product with a moisture content of 24.6%, a ratio of m: n: K: B: 35: 6: 35: 24. Yield 61.0 g (90.4%). :

Pru m ie r 2. 60.g Dowex 1 OH anion exchanger (DVB 8%, exchange capacity 1.7 mEq / g moisture 42%) in 100 ml of 20% acetic acid is stirred 30 n at room temperature pe, filtered, washed with cold water on the filter until neutral wash water, cooled to -2 ° C. added cold (1 ° C) solution of 7.74 g of iodic acid in 60 ml of distilled water, stirred in the cold (from 0 to 2 C) to pH, wash with cold water until neutral wash water, the combined filtrate is evaporated, return 0.04 g of iodic acid dihydrite. A glass filter gives a product with a moisture content of 26.1% and a ratio of m: n: K: B of 22.30: 8: 43.6: 26.1. Stored at (-4) - (20) ° С. Example 3. 600 g of anion exchanger AB-17-8hc "OH (DVB 8%; exchange capacity 1.7 mEq / g, humidity 44%) are mixed with 600 ml of 20% acetic acid for 30 minutes at room temperature Ature, filter, wash with water on the filter until the neutral reaction of the wash water, cool down and add a cooled () solution of 46.44 g of iodic acid in 320 ml

distilled water, mix

to pH 2.2, filtered. in the cold (from O to), rinse with cold water, the combined filtrate is evaporated, return 0.44 g of iodic acid dihydrate. A product with a moisture content of 32.4% and a ratio m: n: K: B of 12: 8: 48: 32 is obtained on a glass filter. Yield 611 g (99.0%). Store t at (-4) (-20C).

Example 4. 60 g of Dowex 1 OH anion exchange resin (DVB 10%, granulation 200-400 mesh, exchange capacity

1.7 mg eq / l, humidity 42%) in 100 ml of 20% acetic acid is stirred for 30 minutes at room temperature, filtered, washed with cold water on a filter until neutral reaction with industrial water and solution 10 is added at 10 ° C. , 7 g of iodic acid in 80 ml of distilled water, stirred to pH 2/8, filtered, washed with water at 18 ° C until neutral

wash water, the combined filtrate is evaporated, return 0.07 g of iodic acid dihydrate. On a glass filter, a product with in: n: K: B "9.7: 10: 48.3: 32 is obtained. Yield 60.1 g ()

content of 0.35 mmol / g.

Examples 5-9, carried out under conditions of example 1, but with different ratios t: n: K: B, are listed in Table 1. Since during the drying time at room temperature (24 hours above vacuum) the Yuff anion is reduced to 10 in the IR spectra of the periodates taken in potassium bromide tablets, a strong absorption band is observed.

neither at 740-770 corresponding to the oscillation frequency of the Hz anion, the anion of 10f corresponds to the vibration frequency at 791 cm.

Application of periodates. -.

For selective oxidation of substrates containing ribosides, periodates: Formulas I are mixed with solutions of substrates, brought to the required temperature, mixed for a specified time, the anion exchangers are filtered and regenerated. The filtrate and the washings are evaporated, the resulting oxidation products are introduced by known methods.

The selectivity of the effect of periodates is illustrated by examples 10 and 11 and Table 2.

PRI im im 10. Selective oxidation of riboside in the presence of

glucoside. 1.0 g of the product obtained according to example 1 is mixed with a solution containing 10 mg of inosine and 10 ml of 1-Hag1-glucopyranosyl-5-fluorouracilide in 5 cl of distilled water, stirred at 30 minutes, from the filter (washed), washed ( 1 Oil ml) with water, evaporated to a volume of 1 ml, divided into Kiezdgel 60 F 254 plates in the n-butanol-ethanol-water system (4: 1: 5). 9- (2-hydroxymethyl-3-oxapentadial-1 is obtained , 5 -yl-4) hypoxanthium monohydrate (inode) .7.48 mg (75.4%). Rf 0.52. UV spectrum, Ig (b): 248 cm- (4.09 1 -B-glucopyranosyl- 5-torouracil is formulated unchanged, yield 8.2 mg (82X). Rf 0.47, System for ethyl acetate-me Anole (20: 3) Rf 0,3.

I. , . Pr and mr 11 g Election

riboside oxidation in the presence of galactoside. 1.0 g of the product obtained in example 3 is mixed with a solution containing 10 mg of inosine and

10 mg of 1-0-met1SH-β-p-galactopyranoside in 5 ml of distilled water, stirred at min., Filtered, washed (lOirl ml) with water, evaporated to a volume of 1 ml. Divided on Knselgel 60 F 254 plates in the n-butanol-s-tanol-water system (4: 1: 5) 9- (2-oxnmethyl-3-oxa-pentadial-1, 5-yl-4) hypoxanthine monohydrate (monk) is obtained. Yield 7.16 mg (72.2%), Rf 0.52. UV spectrum. o, fc lg (6) j 248 (4.09). According to the literature 4 Rf 0.52. 1-0-Methid-A-D-galactopyranoside was isolated unchanged, yield 8.3 mg (83%), Rf 0.2.

In addition to selective riboside oxidation, immobilized periodates can be useful in the rapid quantitative separation of thorium (Th) from uranium (U) VI, in the production of pure homogeneous interferon with a molecular mass of 15000, and in other industries associated with the use of periodates.

Obtain no immobilized trays. Wash the periodate additionally dry in a desiccator.

t a o l n c a t over calcined scoric calcium.

Inosine oxidation by immobilized periodates

1160720

10 Table 2 At optimal ratios of 10.- DVB - CRjCOO (w: n: K: C) "35: 6: 35: 24 h9, 7: 10: 48.3: 32, the output of the inox will be 60Z. The optimal kept woman in DVB anion exchange resin 8Z. drying the immobilized periods leads to a partial reduction of 104 Lo 10} and a sharp decrease in the yield of Nox.

Claims (2)

1. Immobilized periodates of the general formula '- {ffbf ^ - [ffbf ₂ ^. . ncn, CH-B (CH ₃ ) ₃ CH ₃ COO 'Chsn-sn ^ Dn ^ M _r CH (CH _{3) 3} U ₄ with a ratio w: n: K: B of 35: 6: 35:: .24 to 9.7: 10: 48.3: 32 for selectively oxidizing ribosides. 2. The method of obtaining immobilized periodates, which consists in the fact that an aqueous solution of iodic acid is mixed with acetic acid with a strongly basic anion exchange resin and chloromethyl alcohol and aminated trimethylamine copolymer of styrene with 6-105? divinyl benzene and when the ratio of M4 and WS ₃ COO ions is 1: 1-5, at temperatures from -1 to +20 С and pH? 5-3.0. ' §