DE1470360A1 - Process for the production of naturally absent purine nucleosides - Google Patents

Description

The invention relates to a process for the production of purine nuoleosides which do not occur naturally. The purine nucleosides prepared according to the invention have the formula where A = H, -OH or -NH2g B = H, halogen, -SH, -NH2, -NH- (alkyl), or-NH- (acyl)} X = CH or N; R = pentosyl, such as ribosyl or deoxyribosyl, but X is not CH if A = H and B = NH2, and the alkyl radical is a lower alkyl radical with up to 6 carbon atoms and the acyl radical is a lower carboxylic acid radical with up to 7 carbon atoms. Purine nuoleosides which can be produced according to the invention are, for example, purine riboside, 6-meroaptopurine riboside, 2-aminopurine riboside, 2,6-diaminopurine riboside, kinetin riboside (ie 6-furfurylaminopurine, 6-furfurylamino-purine, 6-iodopurine-ribosid-iodopurine, 6-methylamino-purine-iodine-riboside, 6-methylaminopurine-iodine-riboside, 6-methylaminopurine 8-azaguanine riboeid, 6-meroapto-8-azapurine riboside and the corresponding deoxyribosides.

These purine nuoleosides are referred to here as non-naturally occurring (or non-existent), since in nature they, for example, all constituents of nuoleic acids, do not occur in large quantities.

The aforementioned non-naturally occurring purine uoleosides are known to be useful and valuable chemical or biochemical agents in enzymatic and biochemical studies. While the naturally occurring Purine Nuoleosides, such as adenosine, guanosine, xanthosine and inosine, are easily made let, e.g. B. duroh hydrolysis of ribonucleic acids or deoxyribonuoleic acids with formation of a mixture of nuoleosides and separation of the individual nuoleosides with or without deamination or duroh desphosphorylation of purine nuoleotides with the help of phosphatase can the above, not naturally occurring Purine nucleosides are not made from nucleic acids, rather it just is possible with chemical syntheses, the many reaction stages and exact adherence the reaction conditions require. With all previously known chemical processes for the preparation of these nucleosides it is difficult to carry out the reaction so that it takes place at the desired positions of the base and the ribose or deoxyribose. Furthermore, the handling of the labile ribose or the even more labile deoxyribose difficult. A satisfactory synthetic method for the preparation of purine deoxynucleosides in the technical MaSetab has not yet become known.

It has now been found that many aerobic bacteria form enzymatic breaths, which are capable of a ribosyl or deaoxyribosyl group of a nuolsoside in the 9.

Position of a purine base with the formation of a purine nucleus, whose base corresponds to the Purinbaae used. It has been found forner that the transfer of the ribosyl or deoxyribosyl group capable of Bnsymeystome less contain a kind of Phoephorylass because the presence of a phosphate for the Effect of the enzyme systems is necessary. lut become the basis of this knowledge according to the invention, the above-mentioned, non-naturally occurring purine nuoleosides, in particular Purindesoxyribonuoleoaide, the formula (I) from the corresponding Purinbaae duroh the action of the enzyme system produced by aerobic Bokterlon, being reiohlioh and cheap erbZltlloho Nuoleoside or uolootide ale Lieferent of the Ribosyl- or Deoxyribosyl group, d. H. the pentosyl group, for the synthesis of the desired valuable nuoleosides can be used.

Naturally occurring nuolooeido or nuoleotides can be lase duroh hydrolysis of nucleic acids. tinous purine 5'-nuoleotides are for example used as ourson, while the pyrimidine nuoleotides are nowhere near of interest like the valuable purine nucleotides. These less valuable pyrimidine nucleotides are of course well suited as starting material for the process of the invention, d. H. as a supplier of the ribosyl or deoxyribosyl group. As a supplier of the ribosyl group For example, ribonucleobides (e.g. adenosine, inosine, guanosine, uridine and Cytidine) and these ribonucleosides corresponding 2'-, 3'-, 5'-, 2 ', 3'- or 3 ', 5'-ribonuoleotide in question, while as a supplier of a deoxyribecyl group for example Deoxyribonucleosides (e.g. adenine deoxyriboside, hypoxanthine, deoxyriboside, ouanine deoxyriboaid, Cytosine deoxyriboside and thymine deoxyriboside) and these deoxyribonucleosides corresponding 3'-, 5'- or 3 ', 5'-deoxyribonucleotides are suitable. Dieas Nucleoside and / or Nuoleotide can of course also be used as a mixture and then added not to be pure.

The other starting material is the Purinbaae, which corresponds to the base component of the desired purine nucleoside, and to which a ribosyl or deoxyribosyl group is transferred. This purine base has the general formula in which A, B and X have the same meaning as in formula (I). Suitable purine bases are, for example, purine, 2,6-diaminopurine, 2-aminopurine, 6-mercaptopurine, 6-chloropurine, 6-iodopurine, benzoyladenine, 2-amino-6-acetylaminopurine, isoguanine, kinetin, 6-methylaminopurine, 6-ethylaminopurine, 6-isoprop [ylaminopurine, 6-hexylaminopurine, 8-azaguanine, 6-meroapto-8-azopurine, and 6-butyroylamino-8-azapurine.

The aerobic bacteria that are able to form the desired enzyme system are widespread without Ruokaioht on the classification and come for example in the genera Aerobaoter, Aeromonas, Bacillus, Bacterium, Corynebacterium, Erwinia, Esoheriohia, Protes, Pseudomonas, Salmonella, Serratia and Vibrio. For the purposes For example, the following species are preferred according to the invention: Aerobacter aerogenes (Kruse) Beijerinok Aeromonas hydrophila (Chester) Stanier Baoillus brevis Migula emend. Ford Baoillus negaterium de Bary Baolllua aphaerious Neide Baoillus subtilis Cohn emend. Prazmowski Baoterium oadaverin Gale et Epps Corynebacterium sepedonicum (Spiek. et Kott.) Skaptason et Burkholder Erwinia aroideae Townsend Holland Escherichia ooli var. Communiur (Topley et Wilson) Yale Proteus vulgaria Hauser Salmonella enteritidis (Gaertner) Castellani et Chalmers Serratia maroesoens Bizio Pseudomonas putrefaciens (Derby et Hammer) Long et Hamner Vibrio peroolans Mudd et Warren In the method according to the invention, the culture liquid can contain the Bacteria are used directly as an enzyme source, or the cells can be used in Used in the form of a suspension in water, a buffer solution or a saline solution will. The separated cells can also undergo a pretreatment before the reaction be subjected to e.g. B. a destruction by sonicating, grinding with glass balls, treatment with a destructive agent such as phenol, sodium deoxycholate, etc., or washing with an organic solvent such as acetone or ethyl acetate. That The method according to the invention can also be carried out in such a way that the aforementioned aerobic bacteria under aerobic conditions in a suitable culture medium, that contains both raw materials.

The bacteria are incubated in a suitable culture medium under aerobic conditions. The culture medium must have assimilable carbon sources and nitrogen sources containing the Eacterlon used. That is useful Addition of inorganic salts and trace elements. Ala nutrients for incubation come the general substances used for this purpose in question. Ooelgnoto Kohlonstoffquellon are for example starch, soluble starch, dextrin, Glucose, sucrose, lactose, maltose, glycerin. Suitable sources of nitrogen are for example peptone, meat extract, yeast extract @ soybean meal, corn steep liquor, Gluten, sodium glutamate, urea, ammonium salts (e.g. ammonium chloride, ammonium sulfate, Ammonium nitrate, aonium laotate) and nitrates (e.g.

Sodium nitrate, potassium nitrate). Further inorganic salts are for example Potassium phosphate, magnesium sulfate, sodium chloride and calcium chloride. Ale trace elements boric acid, copper sulfate, ferric chloride, manganese sulfate, sodium molybdate and zinc sulfate were used.

The soil conditions under which the aerobic bacteria are incubated are matched to the type of bacteria and / or the culture medium used. Usually the incubation is at a temperature of 2D to 40 0C for a period of 6 days carried out.

In the method according to the invention, the desired purinase of the general formula (II) on the one hand and one or more Nuoloosldo and / or Xunlootldo as a supplier of a ribosyl or deoxyribosyl group on the other hand don bacterial cells odor dom formed by the bacteriaon enzyme system merged. In this reaction, the pH of the medium is preferably between about 4 and 10, but in some cases a pH of 5.0 to 8.0 may be required be. The temperatures are usually in the range of about 20-50 ° C.

The presence of a phosphate is essential for the pentosyl transfer reaction necessary. In some cases where, for example, the enzyme source is associated with the Phosphate is contaminated, or in which Nuoleotide as a pentosyl supplier together Used with phosphomonoesterase or pyrophosphatase is the phosphate additive unnecessary. The phosphate concentration in the reaction mixture is expediently 0.1 to 100mMol, however, a too high photophat excess can have a detrimental effect on the formation of the desired purine pentosides.

The desired purine fuels enriched in the reaction medium There are no known methods that are used to separate the product from fermentative Reactions avez the reaction mixture or for the separation of several similar compounds are applied in the Zinselverbindungen, isolated. For example, the separation by taking advantage of the difference in malignancy in different solvents between the desired connection and the impurities, the difference in the distribution coefficient between the two solvent layers, des Difference in the adsorbability on Msorptionasittoln, such as activated carbon or Ion exchange ohhavr.-zen, the difference in dialysability by a semi-durohaaige Membrane or dea Uhteraehiedea in the Kriatalliaierbarkeit sua a solvent as well as by filtration or centrifugation dea reaction agemiaohea with or without Addition of filter aids takes place. In practice, these methods are used for Laolierung Depending on the desired purity and the condition of the products in combination or carried out repeatedly.

In the following documents, the quantities are also given on the Weight. The strains of aerobic bacteria used in the experiments were also included Amerioan Type Culture Collection (ATCC), Washington, D. C., at Northern Utilization Reaearoh Branoh, U.S. Department of Agrioulture (NRRL), Peoria, III., U.S.A., and deposited with the U.S. Department of Agrioulture (USDA) and bear the background numbers, which consist of the abbreviations mentioned above with a number.

Example 1 Aeroboter aerogenes (Kruse) Beijerinck (@ TCC-9621) The 1% glucose was cultivated overnight at 28 ° on a Boulillon agar medium Contained twenty-five 200 cm3 flasks, each containing 40 cm3 of an aqueous culture medium were inoculated with the cells, with one transmission in each case with one Eyelet was made. The medium beatand from dextrin (20.0 g), polypeptone (10, 0 g), meat iso extract (10.0 g), dipotassium hydrogen phosphate (1.0 g), sodium chloride (5.0 g) and sterilized tap water (1 1) and was kept at pH 7.2. The inoculated medium was incubated for 2 days at 28 ° C. with shaking. After incubation all of the culture fluid was centrifuged to separate the cells. the Cells were washed with 0.8% saline aqueous solution and used for preparation the enzyme source suspended in distilled water (200 cm3).

A Gemisoh from an aqueous solution (0, 2 cm3), the 5 mmol of the in table 1 contained base, an aqueous solution (0.5 cm3) containing 10 mmol 5'-thymoidylic acid, a 1.0 molar acetate buffer solution (0.1 cm3) at pH 5, 75, the enzyme source produced in the flat-eared tit (0, 05 on3) and water (0.15 cm3) was 60 resp.

Maintained 120 minutes at 37 ° C, whereupon the conversion of the bases to the corresponding Nuoleosiden was determined in%. The results are in the table 1 called.

Table 1 Base conversion,% base conversion% 60 minutes 120 minutes 2,6-diaminopurine 68, 2 74.2 6-mercaptopurine 65, 6 75.7 purine 74, 77.5 2-aminopurine 68, 9 76.0 benzoyladenine 66.9 69.8 Kinetin 57. 6 51, 5 8-Asaguanine 7, 6 10, 6 8-Azahypoxanthin n 9.3 10.0 Example 2 Erwinia aroideae (Townsend) Holend (ATCC-15390) was grown for 2 days at 28 ° cultured on a broth agar medium containing 1% Oltooae. A watery one Culture medium (250 cm3) in a 1 1 flask was added to the cells in an amount of 7 sen inoculated. The medium had the same composition as that according to the example 1 medium used. Incubation was carried out for 3 days at 32 ° C. with a shake. Then, kinetin and 5'-thymidylic acid in such amounts became the culture liquid indicate that the concentration was 5 mmol and 25 mmol, respectively.

The culture liquid was adjusted to pH 6.2 with acetic acid. The incubation was continued for 3 hours at 52 ° C, whereupon the culture liquid was centrifuged to separate the solids.

The above liquid was adjusted to pH 4.5 with hydrochloric acid and given a column filled with activated charcoal. The activated carbon was mixed with water washed and eluted with 50% ethanol containing 1.4% ammonia. The eluate was concentrated under reduced pressure, with aqueous ammonia adjusted to pH 11 and duroh. given a column with quaternary bu ohm Polystyrene ion exchange resin (formate form) was filled.

The column was filled with a formic acid-ammonia buffer solution from pH 8.2 eluted. The eluate was subjected to freeze drying, with 253 mg of kinetin deoxyriboaid were obtained.

Example 3 In the manner described in Example 1, an enzyme source was established made from Aerobaoter aerogenes (Kruse) Beijerinck (ATCC-9621).

A mixture of 40 cm3 of an aqueous solution containing 25 mmol of 6-mercaptopurine contains, 20cm3 of an aqueous solution containing 200 mmol of 5'-thymidylic acid, 10 cm3 of a 1 molar acetate buffer solution with a pH of 5, 75 and 30 om the enzyme source was kept at 37 ° C for 3 hours. After the reaction, the Gemisoh sur separation centrifuged from precipitates. The clear liquid became in the usual way treatment with activated carbon, chromatography with ion exchange resin and finally subjected to freeze-drying, whereby powdered 6-mercaptopurine deoxynuoleoside was obtained in a yield of 192 g.

Example 4 The same reaction as in Example 4 was carried out however, deoxy-5'-guanylic acid was used instead of 5'-thymidylic acid. 170 mg of 6-meroaptopurine deoxyriboside were obtained as the product.

Example 5 Vibrio peroolans Mudd et Warren (NRRL, S-31) was obtained from Yacht cultivated at 28 ° on a bouillon agar medium, the Contained 1% glucose. The bacteria cells were inoculated for 1 1 minutes in culture media which had the same composition as the medium used in Example 1.

This was followed by incubation for days at 28 ° with shaking. Thereafter the entire culture liquid was centrifuged to separate the cells. the Cells washed with a 0.8% aqueous saline solution and in a distilled Suspended water (200 cm3) to provide the source of enzyme.

A mixture of 10 cm3 of an aqueous solution containing 20 * moles of 2-aminopurine or 2,6-diaminopurine, 10 cm3 of an aqueous solution containing 60 mmol of thymidine contained, 2 eNT of an aqueous solution containing 0.5 mol of dipotassium hydrogen phosphate, 8 or3 of a 0.5 molar Tris buffer solution with a pH of 8.0 and 10 cm3 of the enzyme source was kept at 37 ° for 2 hours, with 90% of the 2-aminopurine and 82% of the 2, 6-diaminopurine were converted into the corresponding deoxyribonuoleosides.

Example 6 Erwinia eroideae (Towneend) Holland (ATCC-15390) Cultivated for 2 days at 28 ° C. on a broth agar medium containing 1% glucoae. A K (250 or) in a 1 l flask was inoculated with the cells @@ (7 loops).

The medium had the same composition as that in Example 1 medium used. Then incubation took place for 4 days at 28 ° C with shaking. Since 200 omr of the culture liquid is centrifuged to separate the Z @@@@@ n. The cells were washed with 0.8% saline solution and used for preparation the Enzy @@@ elle suspended in distilled water.

A mixture of 0.2 oS an aqueous solution containing 5 mmol of the in The bases mentioned in Table 3 contained, 0.5 c "of an aqueous solution containing 5 sol inosine contained, 0, 1 om) a 1 molar acetate buffer solution with a pH value 5.75 (containing 10 sol potassium dihydrogen phosphate) and 0.2% of the enzyme source was kept at 37 ° C. for 120 minutes and 60 minutes, whereupon the conversion of the bases to the corresponding ribosides was determined in%. Those mentioned in Table 3 Results were obtained.

Table 3 Base conversion in% 60 minutes 120 minutes 2,6-diaminopurine 62 90 6-Meroaptopurine 64 72 Kinetin 25 46 Purine 57 65 2-Aminopurine 49 54 Benzoyladenine 4 17 E Example 7 In the manner described in Example, a source of enzyme was selected Aeroboter aerogenes (Kruse) manufactured by Bei @erinck (ATCC-9621).

A mixture of 0.2 om3 of an aqueous solution containing 5 mPol of the in Table 4 contained bases, 0.5 oar of an aqueous solution containing 5 dol ouanosine contained 0.2 on3 of a 1 molar acetate buffer solution with a pH of 5.9 (the 10 SMol Potassium dihydrogen phosphate) and 0, 1 om3 of the enzyme source was 80 minutes kept at 37 ° C, whereupon the conversion of the bases into the corresponding ribosides semiquantitatively was determined by paper chromatography.

The results are given in Table 4 accordingly.

Table 4 Base conversion x 2,6-diaminopurine +++ 6-meroaptopurine +++ 8-azaguanine + kinetin +++ 2-aminopurine +++ purine +++ benzoyladenine ++ * the level of turnover is marked with +++ if it was in the same amount as at the conversion from adenine to adenosine (about 78). A lower turnover is the closer to the visual Diohte of the color under UV light expressed on the chromatogram with ++ or +.

Example 8 Erwinia aroideae (Townsend) Holland (ATCC-15390) cultivated overnight at 28 ° C on a broth agar medium containing 1% glucose contained. A culture medium (250 cm3) in a 1 l flask was mixed with the cells (1 Eyelet). The medium had the same composition as that in Example 1 Medium used, The incubation was carried out for 4 days at 28 ° C on a rotating platform device carried out. Then, 200 am3 of the culture liquid was used to separate the cells centrifuged. The cells were washed with a 0.8% aqueous saline solution and suspended in distilled water (50 am3) to produce an enzyme source.

A Gemisoh from 30 cm3 of an aqueous solution containing 5 mmol of 2,6-diaminopurine contained 10 om3 of an aqueous solution containing 10 mmol of 5'-cytidylic acid, 10 om3 of an aqueous solution containing 10 mmol of 5'-uridylic acid, 100 om3 one 0.2 molar tris-maleate buffer solution with a pH of 5.6 and 50 cm3 of the enzyme source was kept at 37 ° C for 15 minutes, with 38.8% of the 2,6-diaminopurine in 2,6-diaminopurine ribonuoleoside were converted.

Example 9 The enzyme source prepared according to Example 8 was used.

A mixture of 0.5 cm3 of an aqueous solution containing 5 mol of uridine contained, 0.2 cm3 of an aqueous solution containing 5 mmol of 2-aminopurine, 0, 1 cm3 of a 1 molar acetate buffer solution with a pH of 5.75 (the 10 mmol potassium dinydrogen phosphate contained) and 0.2 cc of the enzyme source was held at 37 ° C for 120 minutes with 54 % of the 2-aminopurine was converted to 2-aminopurine riboside.

Example 10 Aerobot aerogenes (Kruse) Beijerinck (ATCC-9621) The 1% oil is cultivated on a broth agar medium at 28 ° C contained. A culture medium (100 om3) in a 500 omr flask was added to the cells vaccinated (1 loop). The medium had the same composition as that in example 1 medium used. The cells were incubated for 2 days at 28 ° C. with shaking. The cells were separated, washed with an 8% aqueous saline solution and suspended in distilled water (80 cm3) to produce the enzyme source.

A mixture of 0.5 am3 of an aqueous solution containing 5 mmol of uridine contained 0.2 cm3 of an aqueous solution, the 5 mmol of that mentioned in Table 5 Bases contained, 0, omr of a 1 molar acetate buffer solution of pH 5.75 (the 10 Sol potassium dihydrogen phosphate) and 0.2 cm3 of the enzyme cell was 120 minutes kept at 37 ° C, whereupon the use of the Saxon su the corresponding Nuoleosiden was determined in%. The results are given in Table 5.

Table 5 Base conversion in% after 120 min.

2, -Diaminopurine87 6-Meroaptopurine 73 Purine 64 Benzoyladenine 42 Example 11 The Nikroorganiamn mentioned in Table 6 were Uber Naoht at 28 ° C to a Cultivated boillon agar medium containing 1% olucose. With don cells (1 se) a culture medium (40 cm3) was inoculated, which had the same additional moisture as dan Kulturedlw used in Example 1. The incubation was 2 days at 28 ° C under Shaking carried out. The cells were separated and washed with a 0.8% aqueous Washed with saline solution and in distilled water to prepare the enzyme source (50 cm3) suspended.

A mixture of an aqueous solution (1, 0 cm3) containing 5 mmol of the contained purine bases mentioned in Table 6, an aqueous solution (2.5 cm3) which 5 drlol cytidine deoxyriboside contained, a 0.5 solar Tris buffer solution (1 om3) of pH 7.5 (containing 10 mmol of phosphate buffer solution) and the above Enzyme source (0.5 cm3) was kept at 37 ° C for 60 minutes.

After the reaction, the pH of the mixture was reduced with acetic acid Cooling set to 5.0 with Up. the obtained precipitate removed by centrifugation. Activated carbon became the liquid (2a) above (300 mg) given. The mixture was cooled with Vis for 1 hour.

The activated carbon was separated by centrifugation, washed with water and combined with a 5% aqueous perchloric acid solution (3cm3). The mixture was boiled for 60 minutes and then centrifuged, with the above liquid was separated. The original precipitation was carried out with a 5% aqueous perchloric acid solution washed. The wash liquid became with the liquid from the first centrifugal separation united. The conversion of each purine base into the corresponding deoxypurine nuoleoside was determined by wetting with diphenylamine and subsequent colorimetry. The results obtained are shown in Table 6.

Table 6a Microorganism conversion of 6-chloro-6-iodine-6-methyl-isopurine purine aminoguanine purine A) Aerobacter aerogenes (Kruse) Beijerinck (ATCC-9621) 84 81.5 71.5 27.5 B) Erwinia aroideae 10.5 (Townsend) Holland (ATCC-15390) 10 11.5 55 C) Pseudomonas putrefaciens (D. et H.) Long et Hammer (AtCC-8071) 88 79 77.5 29.5 D) Vibrio percolans (Mudd et Warren (NRRL, S-31) 77 78 76 -E) Aeroonas hydrophila (Chester) Stanier (NRRL, B-909) 57.5 54 62.5 -F) Baoillus revis Migula emend. ford (ATCC-9999) 27, 5 31 38 G) Bacillus sphaericus Neide (USDA-344) 43 41.5 47 -H) Baoterium oadaveris (ATCC-9760) 54 55 18 I) Corynebaoterium Sepedonioum (Sp. et K.) Skaptason et Burkholder (ATCC-15391) 28 29 40 -The sign "-" in the last column means that the connection was not keen.

Table 6b Conversion (%) of microorganism E F G H I 6-meroaptopurine 43 41 62 61 48 Purine 82 48 73 8o49 2-aminopurine 68 42 71 68 46 2,6-diaminopurine 59 42 70 6247 Kinetin 81 50 75 72 38 Benzoyladenine 50 36 42 44 24 Example 12 Auf in the manner described in Example 11, various purine bases were mixed with uridine implemented instead of cytidine deoxyriboside, those listed in Table 7 Results were obtained. The same microorganisms are found with the Buchatabon as indicated in Table 6.

Table 7 Conversion (%) of microorganism A B C D E F G H I 6-chloropurine 72 45 82 75 64 32 52 50 25 6-iodopurine 68 40 78 75 58 32 54 54 27 6-methylaminopurine 52 35 75 72 60 40 50 20 38 Isoguanine 28 52 29-6-Mereaptopurine ---- 75 32 68 58 41 Purine ---- 89 58 75 72 52 2-aminopurine ---- 87 55 77 62 48 2,6-diaminopurine ---- 78 49 72 59 45 Kinetin ---- 91 57 78 72 4o Benzoyladenine ---- 42 37 44 42 22 The sign "-" means the connection has not been tested.

Claims (8)

Claims 1. A process for the preparation of purine nucleosides, characterized in that one purine bases of the general formula wherein a) X-CH A-OH or -NH2 b = H, a halogen, -3H, -NH @, -NH- (lower alkyl), or-NH-Aoyl or b) x = N A-Ho OH or- B ii, an alo en, ~ NH-CHf v -SH, -NH2, -NH- (lower alkyl), or-NH-Aoyl or o) x = CH A = HB = H, a halogen, -SH, -NH- (lower alkyl), or -NH-Aoyl and here the alkyl radical is a lower alkyl radical with up to 6 carbon atoms and the aoyl radical is a lower carboxylic acid radical with up to 7 carbon atoms, with naturally occurring purine nuoleosides, purine nuoleosides, pyrimidine deoxyribonuoleosides, pyrimidine deoxyribonuoleosides, pyrimidine deoxyribonuoleosyl groups and pyrimidine deoxyribonuoleosyl groups and / or pyrimidine deoxyribonioosyl groups, or pyrimidine deoxyribonioosyl groups Compounds lying in an aqueous medium with a pH value of 4 to 10 at temperatures between 20 and 50 ° C in the presence of an inorganic phosphate and an enzyme system of the following aerobic bacterial strains that transfer the pentosyl group: Aerobaoter aeorgenes (Kruse) Beijerinck, Aeromonas hydrophila (Chester) Stanier , Jaolllu brerlo Migula emend. Ford, Baeillus sphaerious Neide, Besterium oadaveris Gale et Epps, Corynebaoterium sepe @ onioum (Spiek. Ot Kott.) Akaptson ot Burkholder, Erwinia arodea @ (Towmwwnd) Holland, Pseudomonas putrefaoiens (Derby et Hammer) per Long et Hammer, bruddio et Warren, brings together. S. The method according to claim 1, characterized in that with concentrations of the inorganic phosphate worked in the reaction medium between about 0.1 and 500 mmol will. 3. Kinetin ribocidal. 4. Kinetin deoxyriboside. 5. 2-aminopurine riboside. 6 * 2-aminopurine deoxyriboside. 7. Denzoyladenine riboside. 8. Benzoyladenine deoxyriboside.