Synthesis of Purine Nucleosides from D‐Glucuronic Acid Derivatives and Evaluation of Their Cholinesterase‐Inhibitory Activities

Abstract

Glucuronolactones were used as precursors for N9 and N7 purine nucleosides containing glucuronic acid derivatives in their structures. Acetylated N‐benzylglucofuran‐ and glucopyranuronamides were synthesized in a few steps from glucofuranurono‐6,3‐lactone. They were converted into the corresponding furanosyl and pyranosyl uronamide‐based nucleosides by N‐glycosylation with silylated 2‐acetamido‐6‐chloropurine in the presence of trimethylsilyl triflate. The triacetylated bicyclic lactone was coupled itself with the nucleobase to give bicyclic N9,N7 nucleosides. Tri‐O‐acetylglucopyranurono‐6,1‐lactone was used for the first time as a glycosyl donor for N‐glycosylation, and led to β‐configured N9‐ and N7‐linked purinylglucuronides under reaction conditions similar to those used with the 1‐O‐acetyl‐substituted glycosyl donors. The cholinesterase inhibitory profiles of the synthetic nucleosides bearing glucuronic acid derivatives as glycons were evaluated, and they showed moderate selective acetylcholinesterase inhibitory activities (Ki = 14.78–50.53 μM). The best inhibition was shown by the furanosyl N9‐linked uronamide‐based purine nucleoside.

Synthesis of New Nucleoside Analogues from Theobromine

“…For galacto nucleoside [9], a solution of blocked nucleoside (0.71 mmol) in (47 ml) of 50% aqueous acetic acid was refluxed for 15 min. (10 ml) of water was added and extracted with chloroform (35 ml), then dried over anhydrous Na 2 SO 4 , the solvent was evaporated to give the free nucleoside [12] (0.19 g, 82.6 %) as a yellow syrup.…”

“…To obtain our target the free nucleoside, the protected group was hydrolyzed using sodium methoxide in methanol and aqueous acetic acid for nucleoside [8] and [9 and 10] respectively, forming new free form [11][12][13]. The FT-IR spectrum of these nucleoside showed the appearance of stretching band at (3427-3390 cm 1 ) for hydroxyl group and CH aliphatic of sugar moiety which gives a good indication for formation of free form.…”

“…The FT-IR spectral data for free nucleoside analogues [11][12][13] 11 3427 2930 1634 1701 1562 1361 1071 3618 12 3390 2963 1639 1704 1566 1340 1051 13 3402 2979 2941 1605 1668 1580 1229 1373 1080 1230…”

“…A variety of functionalities have been introduced into either the sugar moiety [3,5] or the heterocyclic moiety [6,7] . Nucleoside analogs represent a potentially important class of antiviral and anticancer agents [8][9][10] with antimicrobial and cholinesterase inhibitory activities [11][12][13][14] and are commonly used to treat hepatitis B virus [15,16] , hepatitis C virus [17] , herpes simplex [18] , Human Immunodeficiency Virus (HIV) and neoplasms [19,20] .…”

“…

Nucleoside Analogues play important role in different medical drugs,therefor we synthesized new nucleoside analogues using theobromine as a nucleobase, for the first time, by convertion to it ' s mercury salt, [1]. Then coupled with three kinds of sugar, including (glucose, galactose and mannose), after protection [2-4] and activation as bromo sugar [5-7] afforded blocked nucleoside analogues [8][9][10] which subsequently hydrolyzed to give our synthetic goal the free nucleoside analogues [11][12][13]. All prepared compounds were identify by FT-IR and some of them with 1 H-NMR spectroscopy.

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