P-D-Arabinofuranosylation

Aquifer bioremediation, defined, 3 758t Aquifer flow, 12 842 Aquifers, 12 838-839 Aquifer sparging, defined, 3 758t AraA [9-(P-D-arabinofuranosyl)-9H-purin-6-amine], 4 713 Arabidopsis, molecular genetics of cellulose biosynthesis, 5 366 Arabinanase, 10 300 Arabinans, classification by structure, 4 723t... 

Schwendener RA, et al. Monograph Alkasar-18, l-(P-D-arabinofuranosyl)-4-octadecylamino-2(lH)-pyrimidin-one, N -octadecyl-ara-C, NO AC. Drugs Future 1995 20 11. 

Schott H, Haussler MP, Schwendener RA. Synthese und eigenschaften von N" -hexadecyl-2 -desoxycytidylyl-(3 -5 )-5-ethyl-2 -desoxy-uridin und 2 -Desoxythy-midylyl-(3 -5 )-N" -hexadecyl-l-P-D-arabinofuranosyl-cytosin, zwei vertreter einer neuen Prodrug-Gruppe. Liebigs Annalen Chemie 1994 277 1994. 

Grant, S., Turner, A.J., Bartimole, T.M., Nelms, P.A., Joe, V.C., and Jarvis, W.D., Modulation of l-[P-D-arabinofuranosyl]cytosine-induced apoptosis in human myeloid leukemia cells by Staurosporine and other pharmacological inhibitors of protein kinase C, Oncol. Res., 6,87,1994. 

C. H. Tann, P. R. Brodfuehrer, S. P. Brundidge, C. Sanino, Jr., and H. G. Howell, Fluorocar-bohydrates in synthesis. An efficient synthesis of l-(2-deoxy-2-fluoro-p-D-arabinofuranosyl)-thymine (P-FMAU), J. Org. Chem 50 3644 (1985). 

Preparation of l-(p-D-arabinofuranosyl)-2-thiocytosine A solution of 2.0 g of l-(2, 3,5,-0-triacetyl-p-D-arabinofuranosyl)-2,4-dithiouracilin 100 ml of methanol is saturated with anhydrous ammonia at 0°C. The mixture, in a glass liner, is heated in a pressure bomb at 100°C for three hours. The reaction mixture is concentrated to a gum in vacuum, and most of the byproduct acetamide is removed by sublimation at 60°C/0.1 mm. The residue is chromatographed on 100 g of silica gel. Elution of the column with methylene chloride-methanol mixtures with methanol concentrations of 2-25% gives fractions containing acetamide and a series of brown gums. The desired product is eluted with 30% methanol-methylene chloride to give a total yield of 0.386 g (30%), MP 175-180°C (dec.). Recrystallization from methanol-isopropanol furnishes an analytical sample, MP 180-182°C (dec.). 

To a solution of 80 mg of l-(p-D-arabinofuranosyl)-2-thiocytosine in 12 ml of water is added dropwise 3 ml of a 1 M bromine solution in carbon tetrachloride. At this point the color of the bromine persists for about 2-3 minutes after each addition. The unreacted bromine is blown off with a stream of nitrogen, and the reaction mixture is concentrated to a syrup in vacuum using a bath temperature less than 50°C. The residue is evaporated three times with 10 ml portions of ethanol, whereupon it crystallizes. The product is triturated with cold ethanol and with ether to obtain 17 mg of 2,2 -anhydro-l-(P-D-arabinofuranosyl)cytosine hydrobromide, MP 240°C (dec.). 

A) Preparation of 1- (2,3,5-Tri-0-Acetyl-p-D-Arabinofuranosyl)-4-Thiouracil A mixture of 1.85 g (5.0 mmol) of l-(2,3,5-tri-0-acetyl-p-arabinofuranosyl) uracil, 1.23 g (5.55 mmol) of phosphorus pentasulfide, and 30 ml of pyridine was heated under gentle reflux for 2.5 hours with exclusion of moisture. The reaction mixture was cooled, and the supernatant solution was transferred by means of a pipette into a mixture of crushed ice and water. The reaction flask was washed twice with pyridine, and these washings were added to the ice-water mixture. This mixture was kept at about 25°C until the ice had melted, and was then stored at 0°C for one hour. A pale yellow precipitate that formed was collected on a filter, washed with ice-water, and dried in air. 

B) Preparation of 1-p-D-Arabinofuranosylcytosine In a glass liner, a mixture of 1.16 g (3.0 mmol) of l-(2,3,5-tri-0-acetyl-p-D-arabinofuranosyl)-4-thiouracil prepared in (A) and about 60 ml of absolute methanol which had been saturated with anhydrous ammonia at 0°C was heated in a steel bomb at 98° to 105°C for 35 hours. After cooling to about 25°C and venting the bomb, the dark solution was filtered into a round-bottom flask. The methanol and excess ammonia were then removed under reduced pressure at about 25°C. The residual syrup was dissolved in absolute methanol, and the methanol was removed under reduced pressure at a bath temperature of about 40°C. This procedure of dissolving in absolute methanol and removing the solvent was repeated, and the residue was held under reduced pressure at a bath temperature of 45°C for 12 hours. 

Chemical Name 9-p-D-Arabinofuranosyl-9H-purine-6-amine monohydrate Common Name Adenine arabinoside Spongoadenosine Structural Formula ... 

In the foregoing procedure, when the temperature of incubation in the two fermentation stages is raised from 25° to 27°C to 36° to 38°C, the same 9-(p-D-arabinofuranosyl)adenine product is obtained in higher yields. 

Synthesis of[36CI]-, [82Br]- and [123l]-labelled 1-(3 -chloro-(bromo and iodo)-3 -deoxy-p-D-arabinofuranosyl)uracil... 

Figure 18.9. Enzymatic preparation of a prodrug of 9-P-D-arabinofuranosyl guanine (25).

Compound 25 (Fig. 18.9), a prodrug of 9-P-D-arabinofuranosyl guanine (26), was developed for the potential treatment of leukemia. Compound 24 is poorly soluble in water and its synthesis by conventional techniques is difficult. An enzymatic demethoxylation process was developed using adenosine deaminase (Mahmoudian et al., 1999, 2001). Compound 25 was enzymatically prepared from 6-methoxyguanine (27) and ara-uracil (28) using uridine phosphorylase and purine nucleotide phosphorylase. Each protein was cloned and overexpressed in independent Escherichia coli strains. Fermentation conditions were optimized for production of both enzymes and a co-immobilized enzyme preparation was used in the biotransformation process at 200 g/L substrate input. Enzyme was recovered at the end of the reaction by filtration and reused in several cycles. A more water soluble 5 -acetate ester of compound 26 was subsequently prepared by an enzymatic acylation process using immobilized Candida antarctica lipase in 1,4-dioxane (100 g/L substrate) with vinyl acetate as the acyl donor (Krenitsky et al., 1992). 

Mahmoudian, M., Eaddy, J., and Dawson, M. 1999. Enzymic acylation of 506U78 (2-amino-9-P-D-arabinofuranosyl-6-methoxy-9H-purine), a powerful new anti-leuke-mic agent. Biotech. Appl. Biochem., 29(3), 229-233. 

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