Preparation of Thymidine-4'-C-carboxylic Acid and Its Derivatives

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Title:Preparation of Thymidine-4'-C-carboxylic Acid and Its Derivatives
Creators:
Hřebabecký, Hubert
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 62, 7, pp. 1128-1135
Uncontrolled Keywords:Thymidine-4'-<i>C</i>-carboxylic acid, (3R,2S,5R)-3-Hydroxy-2-hydroxymethyl-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)tetrahydrofuran-2-carboxylic acid

Abstract

3',5'-Di-<i>O</i>-benzoyl-4'-<i>C</i>-hydroxymethylthymidine (<strong>3</strong>) was prepared in four steps from 3'-<i>O</i>-(<i>tert</i>-butyldimethylsilyl)-4'-<i>C</i>-hydroxymethylthymidine (<strong>1</strong>). Oxidation of <strong>3</strong> with pyridinium dichromate afforded 3',5'-di-<i>O</i>-benzoylthymidine-4'-<i>C</i>-carboxylic acid (<strong>4</strong>) which on debenzoylation gave free thymidine-4'-<i>C</i>-carboxylic acid, (3<i>R</i>,2<i>S</i>,5<i>R</i>)-3-hydroxy-2-hydroxymethyl-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)tetrahydrofuran-2-carboxylic acid, (<strong>5</strong>). Esterification of acid <strong>5</strong> with diazomethane afforded the methyl ester <strong>6</strong>. Its isopropyl ester <strong>7</strong> was obtained by transesterification of the methyl ester <strong>6</strong>. Reaction of ester <strong>6</strong> with ammonia and hydrazine led to the respective amide <strong>8</strong> and hydrazide <strong>9</strong>. Upon reaction with 1,1'-carbonyldiimidazole, the protected acid <strong>4</strong> was converted into the corresponding imidazolide <strong>11</strong>, which, without isolation, was treated with glycinamide, dimethylamine and aminoethanol to give aminocarbonylmethylamide <strong>12a</strong>, <i>N,N</i>-dimethylamide <strong>13a</strong> and hydroxyethylamide <strong>14a</strong>, respectively. The free amides <strong>12b</strong>, <strong>13b</strong> and <strong>14b</strong> were obtained by methanolysis of corresponding benzoates with methanolic sodium methoxide. Neither of the prepared compounds exhibited significant activity against HIV.

Title:Preparation of Thymidine-4'-C-carboxylic Acid and Its Derivatives
Creators:
Hřebabecký, Hubert
Holý, Antonín
Uncontrolled Keywords:Thymidine-4'-<i>C</i>-carboxylic acid, (3R,2S,5R)-3-Hydroxy-2-hydroxymethyl-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)tetrahydrofuran-2-carboxylic acid
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:62
Number:7
Page Range:pp. 1128-1135
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19971128UNSPECIFIED
ID Code:1192
Item Type:Article
Deposited On:06 Feb 2009 17:07
Last Modified:06 Feb 2009 16:07

Citation

Hřebabecký, Hubert; Holý, Antonín (1997) Preparation of Thymidine-4'-C-carboxylic Acid and Its Derivatives. Collection of Czechoslovak Chemical Communications, 62 (7). pp. 1128-1135. ISSN 0010-0765

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