Synthesis of N4-Amino and N4-Hydroxy Derivatives of 5-Azacytidine. A Facile Rearrangement of the N4-Amino Derivative to 5-(3-β-D-Ribofuranosylureido)-1H-1,2,4-triazole

[img]PDF - Authorized users only
Language: English
119Kb
Title:Synthesis of N4-Amino and N4-Hydroxy Derivatives of 5-Azacytidine. A Facile Rearrangement of the N4-Amino Derivative to 5-(3-β-D-Ribofuranosylureido)-1H-1,2,4-triazole
Creators:
Pískala, Alois
Hanna, Naeem B.
Masojídková, Milena
Fiedler, Pavel
Votruba, Ivan
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 69, 4, pp. 905-917
Uncontrolled Keywords:1,3,5-Triazines, Ureas, Nucleosides, Hydrazones, Antibacterial activity, Cleavage, 1,2,4-Triazoles

Abstract

Treatment of methoxyribosyltriazinone <strong>4</strong> with hydrazine in methanol afforded crude 4-hydrazino-1-β-D-ribofuranosyl-1,3,5-triazin-2(<i>1H</i>)-one (<i>N</i><sup>4</sup>-amino-5-azacytidine) (<strong>2</strong>), which rearranged rapidly to isomeric 5-ribosylureidotriazole <strong>6</strong>. The rearrangement proceeds easily also in water solutions of <strong>2</strong>. Alkaline hydrolysis of <strong>6</strong> gave a mixture of 5-ureidotriazole <strong>7</strong> and 5-aminotriazole <strong>8</strong>. Acid hydrolysis of <strong>6</strong> afforded only <strong>7</strong>. This compound was also prepared by thermal rearrangement of 5-amino-1-carbamoyltriazole <strong>9</strong> or on reaction of cyano(formyl)guanidine <strong>10</strong> with hydrazine hydrochloride. Treatment of benzoylated methoxyribosyltriazinone <strong>4a</strong> with hydrazine in methanol gave only the rearranged product <strong>6a</strong>. Reaction of tribenzoylribosyl isocyanate <strong>12</strong> with aminotriazole <strong>8</strong> gave 1-triazolecarboxamidotribenzoylribose <strong>13</strong>, which afforded by methanolysis oxazoloribofuranose <strong>14</strong> and aminotriazole <strong>8</strong>. Compound <strong>14</strong> was also obtained by methanolysis of blocked ribosylcarbamate <strong>16</strong>. Reaction of methoxyribosyltriazinone <strong>4</strong> with hydroxylamine in methanol afforded 4-hydroxylamino-1-β-D-ribofuranosyl-1,3,5-triazin-2(<i>1H)</i>-one (<i>N</i><sup>4</sup>-hydroxy-5-azacytidine) (<strong>3</strong>), which on the action of excess hydroxylamine yielded 1-cyano-1-hydroxy-5-β-D-ribofuranosylisobiuret (<strong>19</strong>). Treatment of methoxy-1,3,5-triazinone <strong>18</strong> with a solution of hydroxylamine in methanol gave 4-hydroxylamino-1-methyl-1,3,5-triazin-2(1<i>H</i>)-one (<i>N</i><sup>4</sup>-hydroxy-1-methyl-5-azacytosine) (<strong>17</strong>). Heating of cyano(formyl)guanidine <strong>10</strong> with hydroxylamine hydrochloride in water lead to the formation of triuret (<strong>21</strong>). The mechanisms of the reactions of methoxyribosyltriazinone <strong>4</strong> with hydrazine and hydroxylamine are discussed. Compounds <strong>2</strong>, <strong>6</strong> and <strong>19</strong> exhibited no significant antibacterial or cytostatic activity. <p>

Title:Synthesis of N4-Amino and N4-Hydroxy Derivatives of 5-Azacytidine. A Facile Rearrangement of the N4-Amino Derivative to 5-(3-β-D-Ribofuranosylureido)-1H-1,2,4-triazole
Creators:
Pískala, Alois
Hanna, Naeem B.
Masojídková, Milena
Fiedler, Pavel
Votruba, Ivan
Uncontrolled Keywords:1,3,5-Triazines, Ureas, Nucleosides, Hydrazones, Antibacterial activity, Cleavage, 1,2,4-Triazoles
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:69
Number:4
Page Range:pp. 905-917
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20040905UNSPECIFIED
ID Code:2251
Item Type:Article
Deposited On:06 Feb 2009 17:16
Last Modified:06 Feb 2009 16:17

Citation

Pískala, Alois; Hanna, Naeem B.; Masojídková, Milena; Fiedler, Pavel; Votruba, Ivan (2004) Synthesis of N4-Amino and N4-Hydroxy Derivatives of 5-Azacytidine. A Facile Rearrangement of the N4-Amino Derivative to 5-(3-β-D-Ribofuranosylureido)-1H-1,2,4-triazole. Collection of Czechoslovak Chemical Communications, 69 (4). pp. 905-917. ISSN 0010-0765

Repository Staff Only: item control page