Synthesis of 5-Phenyl-2(1H)-pyrimidinone Nucleosides

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Title:Synthesis of 5-Phenyl-2(1H)-pyrimidinone Nucleosides
Creators:
Krečmerová, Marcela
Hřebabecký, Hubert
Masojídková, Milena
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 61, 3, pp. 458-477
Uncontrolled Keywords:Pyrimidines, 5-Phenyl-2(1<i>H</i>)-pyrimidinone base-modified, Nucleosides, Deoxynucleosides

Abstract

Reaction of 2-phenyltrimethinium salt <strong>1</strong> with thiourea and subsequent reaction with chloroacetic acid afforded 5-phenyl-2(1<i>H</i>)-pyrimidinone (<strong>3</strong>). Its silyl derivative <strong>4</strong> was condensed with 1-<i>O</i>-acetyl-2,3,5-tri-<i>O</i>-benzoyl-D-ribofuranose under catalysis with tin tetrachloride or trimethylsilyl trifluoromethanesulfonate to give protected nucleoside <strong>5</strong> together with 5',<i>O</i><sup>6</sup>-cyclo-5-phenyl-1,3-bis- (β-D-ribofuranosyl)-6-hydroxy-5,6-dihydro-2(1<i>H</i>,3<i>H</i>)-pyrimidinone (<strong>7</strong>). The greatest amounts of <strong>7</strong> were formed with the latter catalyst. Nucleosidation of the silyl derivative <strong>4</strong> with protected methyl 2-deoxy-D-ribofuranoside <strong>8</strong> or 2-deoxy-D-ribofuranosyl chloride <strong>9</strong> afforded 1-(2-deoxy-3,5-di-<i>O</i>-<i>p</i>-toluoyl-β-D-ribofuranosyl)-5-phenyl-2(1<i>H</i>)-pyrimidinone (<strong>10</strong>) and its α-anomer <strong>11</strong>. Reaction of <strong>10</strong> and <strong>11 </strong>with methanolic ammonia gave free 2'-deoxynucleosides <strong>12</strong> and <strong>13</strong>. Compound <strong>13</strong> was converted into 5'-<i>O</i>-<i>tert</i>-butyldiphenylsilyl-3'-<i>O</i>-mesyl derivative <strong>14</strong> which on heating with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and subsequent cleavage with tetrabutylammonium fluoride afforded 2',3'-dideoxy-2',3'-didehydronucleoside <strong>15</strong>. Reaction of the silyl derivative <strong>4</strong> with 1,2-di-<i>O</i>-acetyl-3,5-di-<i>O</i>-benzoylxylofuranose (<strong>18</strong>), catalyzed with tin tetrachloride, furnished 1-(2-<i>O</i>-acetyl-3,5-di-<i>O</i>-benzoyl-β-D-xylofuranosyl)-2(1<i>H</i>)-pyrimidinone (<strong>19</strong>) which was deprotected to give the β-D-xylofuranosyl derivative <strong>22</strong>. As a side product, the nucleosidation afforded the β-D-xylopyranosyl derivative <strong>23</strong>. Deacetylation of compound <strong>19</strong> gave 1-(3,5-di-<i>O</i>-benzoyl-β-D-xylofuranosyl)-5-phenyl-2(1<i>H</i>)-pyrimidinone (<strong>24</strong>) which on reaction with thionyl chloride afforded 2'-chloro-2'-deoxynucleoside <strong>25</strong> and 2',<i>O</i><sup>6</sup>-cyclonucleoside <strong>26</strong>. Heating of compound <strong>25 </strong>with DBU in dimethylformamide furnished the <i>lyxo</i>-epoxide <strong>27</strong> which on reaction with methanolic ammonia was converted into free 1-(2,3-anhydro-β-D-lyxofuranosyl)-5-phenyl-2(1<i>H</i>)-pyrimidinone (<strong>28</strong>). Reaction of 1,2-di-<i>O</i>-acetyl-5-<i>O</i>-benzoyl-3-<i>O</i>-methanesulfonyl-D-xylofuranose (<strong>30</strong>) with silyl derivative <strong>4</strong> gave the nucleoside <strong>31</strong> which by treatment with DBU was converted into an equilibrium mixture of 5'-benzoylated arabinofuranoside <strong>33a</strong> and its 2',6-anhydro derivative <strong>33b</strong>. <p>

Title:Synthesis of 5-Phenyl-2(1H)-pyrimidinone Nucleosides
Creators:
Krečmerová, Marcela
Hřebabecký, Hubert
Masojídková, Milena
Holý, Antonín
Uncontrolled Keywords:Pyrimidines, 5-Phenyl-2(1<i>H</i>)-pyrimidinone base-modified, Nucleosides, Deoxynucleosides
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:3
Page Range:pp. 458-477
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19960458UNSPECIFIED
ID Code:949
Item Type:Article
Deposited On:06 Feb 2009 17:05
Last Modified:06 Feb 2009 16:05

Citation

Krečmerová, Marcela; Hřebabecký, Hubert; Masojídková, Milena; Holý, Antonín (1996) Synthesis of 5-Phenyl-2(1H)-pyrimidinone Nucleosides. Collection of Czechoslovak Chemical Communications, 61 (3). pp. 458-477. ISSN 0010-0765

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