[Synthesis]
GENERAL STEPS: (2R,3R,4R,5R)-2-(Acetoxymethyl)-5-(2-amino-6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate (1.56 g, 3.64 mmol) was dissolved in acetone (10 mL), phosphate buffer (58 mL, pH 8) and Novozyme (1.6 g) were added. The reaction mixture was stirred at 60°C for 8 days. After completion of the reaction, the enzyme was removed by filtration and washed with ethanol (50 mL) and acetone (50 mL). The filtrate was concentrated under reduced pressure and the resulting crude product was purified by silica gel column chromatography (eluent: CH2Cl2:MeOH, 85:15) to afford (2R,3R,4S,5R)-2-(2-amino-6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (0.61 g, 55% yield) as a light blue powder.1H NMR ( 400 MHz, DMSO-d6) δ 8.38 (s, 1H, H-8), 6.99 (s, 1H, NH2), 5.81 (d, J = 5.80 Hz, 1H, H-1'), 5.49 (br s, 1H, OH-2'), 5.19 (br s, 1H, OH-3'), 5.05 (t, J = 5.24 Hz, 1H, OH -5'), 4.47 (t, J = 4.85 Hz, 1H, H-2'), 4.20-4.02 (m, 1H, H-3'), 3.90 (q, J = 3.98 Hz, 1H, H-4'), 3.69-3.60 (m, 1H, H2-5'), 3.59-3.52 (m, 1H, H2-5'); 13C NMR (100 MHz, DMSO-d6) δ 160.5, 154.7, 150.2, 141.9, 124.2, 87.4, 86.0, 74.2, 70.9, 61.9; high resolution ES-MS m/z 302.0649 ([M + H]+, C10H1335ClN5O4 calculated value 302.0651). |
[References]
[1] A. JANKOWSKI L. T D Wise. Sodium Thiosulfate and Potassium Selenosulfate as Reagents to Prepare Thio-and Selenopurine Nucleosides[J]. Nucleosides, Nucleotides & Nucleic Acids, 1989, 8 1: 339-348. DOI:10.1080/07328318908054179.
[2] SUNDEEP RAYAT. 5-Cyanoimino-4-oxomethylene-4,5-dihydroimidazole and 5-Cyanoamino-4-imidazolecarboxylic Acid Intermediates in Nitrosative Guanosine Deamination: Evidence from 18O-Labeling Experiments[J]. Journal of the American Chemical Society, 2004, 126 32: 9960-9969. DOI:10.1021/ja049835q.
[3] MORRIS J. ROBINS. Nucleic acid related compounds. 114. Synthesis of 2,6-(disubstituted)purine 2′,3′-dideoxynucleosides and selected cytotoxic, anti-hepatitis b, and adenosine deaminase substrate activities[J]. Journal of Heterocyclic Chemistry, 2009, 38 6: 1297-1306. DOI:10.1002/jhet.5570380609.
[4] KATHLEEN TOO . Anti-malarial activity of N6-modified purine analogues[J]. Bioorganic & Medicinal Chemistry, 2007, 15 16: Pages 5551-5562. DOI:10.1016/j.bmc.2007.05.038.
[5] ALICJA STACHELSKA-WIERZCHOWSKA. Tri-Cyclic Nucleobase Analogs and their Ribosides as Substrates of Purine-Nucleoside Phosphorylases. II Guanine and Isoguanine Derivatives.[J]. Molecules, 2019, 24 8. DOI:10.3390/molecules24081493.
[6] SHIH-HSI CHU Ming Y C Chyng Yann Shiue. Synthesis and cytotoxicity of 6-selenopurine arabinoside and related compounds[J]. Journal of pharmaceutical sciences, 1975, 64 8: 1343-1346. DOI:10.1002/jps.2600640818. |