Synthesis and Enzymic Hydrolysis of Acylated Adenosine Derivatives

Abstract

Various derivatives of adenosine were prepared by acylation of adenosine (6-amino-9-(b-D-ribofuranosyl)purine (1) with different molar equivalents of acetic anhydride and/or pivaloyl chloride in pyridine. Compounds 6-acetylamino-9- (4), and 6-pivaloylamino-9-[(2,3,5-tri-O-pivaloyl)-b-D-ribofuranosyl]purine (5) were subsequently submitted to hydrolysis catalyzed by a number of hydrolytic enzymes. Regioselective enzymic deacetylation at the primary hydroxyl group of 3 and 4 with butyrylcholinesterase (BChE) produced 6-acetylamino-9-[(2,3-di-O-acetyl)-b-D-ribofuranosyl]purine (9) and 6-amino-9-[(2,3-di-O-acetyl-b-D-ribofuranosyl]purine (10), respectively. All structures were established by 1 H and 13 C NMR spectroscopies.

The practical acetylation of nucleosides using acetic anhydride/acetic acid as a reusable solvent

“…174–176 o C (Lit. 18 174–175 o C). 1 H NMR (400 MHz, CDCl 3 ): δ = 8.33 (s, 1H, 2-H), 7.95 (s, 1H, 8-H), 6.18 (d, J = 5.6 Hz, 1H, 1’-H), 6.14 (br s, 2H, NH 2 ), 5.92 (t, J = 5.6 Hz, 1H, 2’-H), 5.66 (t, J = 4.8, 1H, 4’-H), 4.45–4.33 (m, 3H, 3’ and 5’-H), 2.12 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.06 (s, 3H, OAc).…”

“…1 H NMR (400 MHz, DMSO-d 6 ): δ = 10.73 (br s, 1H, NH), 8.31 (s, 1H, 2-H), 7.94 (s, 1H, 8-H), 6.00 (d, J = 6.0 Hz, 1H, 1'-H), 5.80 (t, J = 6.0 Hz, 1H, 2'-H), 5.50 (t, J = 4.4 Hz, 1H, 4'-H), 4.40-4.24 (m, 3H, 3' and 5'-H), 2.12 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.04 (s, 3H, OAc). 13 18 174-175 o C). 1 H NMR (400 MHz, CDCl 3 ): δ = 8.33 (s, 1H, 2-H), 7.95 (s, 1H, 8-H), 6.18 (d, J = 5.6 Hz, 1H, 1'-H), 6.14 (br s, 2H, NH 2 ), 5.92 (t, J = 5.6 Hz, 1H, 2'-H), 5.66 (t, J = 4.8, 1H, 4'-H), 4.45-4.33 (m, 3' and 5'-H), 2.12 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.06 (s, 3H, OAc).…”

Synthesis of a Bioreversibly Masked Lipophilic Adenosine Diphosphate Ribose Derivative

“…[20][21][22][31][32] The analytical data for 5 were identical with those reported before. [33] Synthesis of 5'-O-(PB)-adenosine Ac phosphoramidite (3):T he reaction was performed according to the general procedure A. Compound 5 (42.1 mg, 0.107 mmol, 1.0 equiv) was dissolved in CH 3 CN (1.0 mL), and compound 6 (51.8 mg, 0.118 mmol, 1.1 equiv) was separately dissolved in CH 3 CN (1.8 mL).…”