Synthesis of 5-Phenylcytosine Nucleoside Derivatives

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Title:Synthesis of 5-Phenylcytosine Nucleoside Derivatives
Creators:
Krečmerová, Marcela
Hřebabecký, Hubert
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 61, 4, pp. 645-655
Uncontrolled Keywords:2',3'-Dideoxynucleoside, Nucleosides, Pyrimidine, 5-Phenylcytosine

Abstract

Reaction of silylated 5-phenylcytosine with 1-<i>O</i>-acetyl-2,3,5-tri-<i>O</i>-benzoyl-D-ribose, catalyzed with tin tetrachloride, and subsequent methanolysis afforded 5-phenylcytidine (<strong>2</strong>). This compound reacted with thionyl chloride in acetonitrile to give cyclic sulfite <strong>3</strong> which on heating in dimethylformamide was converted into 2,2'-anhydro-1-(β-D-arabinofuranosyl)-5-phenylcytosine (<strong>4</strong>). Analogous reaction of compound <strong>2</strong> with thionyl chloride at reflux gave 5'-chloro-5'-deoxy-2',3'-cyclic sulfite <strong>5</strong>. Its heating in dimethylformamide afforded 5'-chloro-2,2'-anhydro derivative <strong>6</strong>, mild alkaline hydrolysis led to 5'-chloro-5'-deoxy-5-phenylcytidine (<strong>7</strong>). Alkaline hydrolysis of 5-phenyl-2,2'-anhydrocytidine (<strong>4</strong>) gave 5-phenylcytosine arabinoside <strong>8</strong>, whereas the 2,2'-anhydro derivative <strong>6</strong> afforded 1-(5-chloro-5-deoxy-β-D-arabinofuranosyl)-5-phenylcytosine (<strong>11</strong>). At higher temperature, the final reaction product was 2,5'-anhydro-5-phenylcytidine (<strong>12</strong>). 5'-Chloro-5'-deoxynucleosides <strong>7</strong> and <strong>11</strong> reacted with tri-n-butyl- stannane to give 5'-deoxyribofuranosyl and 5'-deoxyarabinofuranosyl derivatives <strong>15</strong> and <strong>16</strong>. 5-Phenylcytidine (<strong>2</strong>) was converted into the <i>N</i><sup>4</sup>-acetate <strong>17 </strong>with acetic anhydride. Further reaction with acetic anhydride and hydrogen bromide in acetic acid afforded a mixture of peracetylated 2'-bromo and 3'-bromo derivatives <strong>18</strong> and <strong>19</strong>. Reaction with Zn/Cu couple gave 5'-<i>O</i>-acetyl-5-phenyl-2',3'-didehydro derivative <strong>20</strong> and 2',3',5'-tri-<i>O</i>-acetyl-5-phenylcytidine (<strong>21</strong>). Compound <strong>20</strong> was deblocked to 1-(2,3-dideoxy-β-D-<i>glycero</i>-pent-2-enofuranosyl)-5-phenylcytosine (<strong>22</strong>). Catalytic hydrogenation of compound <strong>20</strong> over palladium and subsequent deblocking of the protected 2',3'-dideoxy derivative <strong>23</strong> gave 1-(2,3-dideoxy-β-D-<i>glycero</i>-pentofuranosyl)-5-phenylcytosine (<strong>24</strong>).

Title:Synthesis of 5-Phenylcytosine Nucleoside Derivatives
Creators:
Krečmerová, Marcela
Hřebabecký, Hubert
Holý, Antonín
Uncontrolled Keywords:2',3'-Dideoxynucleoside, Nucleosides, Pyrimidine, 5-Phenylcytosine
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:61
Number:4
Page Range:pp. 645-655
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19960645UNSPECIFIED
ID Code:964
Item Type:Article
Deposited On:06 Feb 2009 17:05
Last Modified:06 Feb 2009 16:05

Citation

Krečmerová, Marcela; Hřebabecký, Hubert; Holý, Antonín (1996) Synthesis of 5-Phenylcytosine Nucleoside Derivatives. Collection of Czechoslovak Chemical Communications, 61 (4). pp. 645-655. ISSN 0010-0765

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