Synthesis of new Nucleoside & Nucleotide Analogues

Ali Al-fatahi, Yousif; Irhaeem Kadhim, Muqdad

	Synthesis of new Nucleoside & Nucleotide Analogues
journal of al-qadisiyah for pure science(quarterly)
Article 1, Volume 12, Issue 1, 2012, Pages 41-57 PDF (0 K)
Authors
Yousif Ali Al-fatahi; Muqdad Irhaeem Kadhim
Abstract
The designed multistep synthetic route to these nucleoside start with diacetone glucose (1 ) prepared in one step from D-glucose [Scheme.A ]. Oxidation of the diacetone glucose (1) with dimethyl sulphoxide and acetic anhydride of the 3-hydroxyl group gave the corresponding ulose derivative (2).Condensation of (2) with nitromethane under PTC condition yielded the nitromethyl derivative (3), which was converted to the derivative (4). Upon treatment with nitromethane in presence of sodium ethoxide. To obtain the first type of nucleoside analogues (18) , (19) , (20 ) and (21 ); isopropyiidene acetal at -5,6-position was removed with acetic acid followed by periodate oxidation and borohydride reduction to give the derivative (9). The 5-hydroxyl group was protected with benzoyl group using benzoyl chloride to give the 5-benzoate derivative (8). Treatment with trifluouro acetic anhydride in the presence of acetic acid gave the 1,2-di-O-¬trifloro acetylated derivative (9). When (9) was allowed to react with mercuric theophylline salt ,mercuric indole salt , silylated uracil and silylated cytosine, the four nucleoside analogues (14),(15), (16) and (17) were obtained.The free nucleoside (18),(19), (20) and (21) were obtained when (14),(15), (16) and (17) were allowed to react with sodium methoxide in methanol.The second type [Scheme. B ] of nucleotide analogues was obtained from the condensation of ethylcanoacetate derivative with (2) to (give the derivative (22), followed by addition potassium cyanide in basic media gave (23 ) .Deprotection of the isopropylidene derivative at 5,6-position followed by periodate oxidation and borohydride reduction in situ gave the ribo derivative (25) .Benzoylation of the ribo derivative (25) with benzoy1 chloride protected the 5-hvdroxyl group to give (26) [Scheme. B ]. Treatment of (26) with acetic acid and trifluoro acetic anhydride gave the 1,2-di-O-¬trifluoro acetylated derivative (27).The condensation of (27)with the mercuric theophylline salt ,mercuric indole salt , silylated uracil and silylated cytosine yielded the nucleotide analogue (28),(29),(30) and (31) respectively .Hydrolysis under basic condition yield the free nucleotide analogue (32), (33) , (34) and (35 ).The synthesized derivatives were characterized by thin layer Chromatography, infrared spectroscopy ,13CNMR ,1HNMR ( nuclear magnetic resonance) .It is hoped that the new synthesized nucleoside and nucleotide analogues may possess antiviral , anticancer and antibacterial activity.

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