Preparation of 5-Benzyluracil and 5-Benzylcytosine Nucleosides as Potential Inhibitors of Uridine Phosphorylase

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Title:Preparation of 5-Benzyluracil and 5-Benzylcytosine Nucleosides as Potential Inhibitors of Uridine Phosphorylase
Creators:
Krečmerová, Marcela
Hřebabecký, Hubert
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 61, 4, pp. 627-644
Uncontrolled Keywords:Uridine phosphorylase, 5-Benzyluracil, Nucleosides, Pyrimidine

Abstract

Reaction of 3,4,6-tri-<i>O</i>-acetyl-2-deoxyglucopyranosyl bromide (<strong>1</strong>) with silylated 5-benzyluracil and subsequent ammonolysis afforded α- and β-anomers of 5-benzyl-1-(2-deoxy-D-glucopyranosyl)uracil (<strong>2</strong> and <strong>3</strong>). Under catalysis with tin tetrachloride, silylated 5-benzyluracil reacted with 1-<i>O</i>-acetyl-2,3,5-tri-<i>O</i>-benzoyl-D-ribofuranose to give 2',3',5'-tri-<i>O</i>-benzoyl-5-benzyluridine (<strong>10</strong>), which was converted into the 4-thio derivative <strong>11</strong> by reaction with Lawesson reagent. Debenzoylation of compound <strong>11</strong> afforded 5-benzyl-4-thiouridine (<strong>12</strong>), whereas its reaction with methyl iodide and deblocking gave 4-methylthiopyrimidine nucleoside <strong>14</strong>. Amonolysis of derivative <strong>12</strong> at elevated temperature afforded 5-benzylcytidine (<strong>15</strong>). This reacted with thionyl chloride at room temperature to give cyclic sulfite <strong>16</strong> which on heating at 100 °C in dimethylformamide was converted into 5-benzyl-2,2'-cyclocytidine (<strong>17</strong>). Mild alkaline hydrolysis of compound <strong>17</strong> afforded 1-(β-D-arabinofuranosyl)-5-benzylcytosine (<strong>18</strong>). With boiling thionyl chloride, compound <strong>15</strong> formed 2',3'-cyclic sulfite <strong>19</strong> which on alkaline hydrolysis gave 5-benzyl-5'-chloro-5'-deoxycytidine (<strong>20</strong>). Compound <strong>20</strong> was reduced with tributylstannane to 5-benzyl-5'-deoxycytidine (<strong>21</strong>). Reaction of silylated 5-benzyluracil with 2-deoxy-3,5-bis(<i>O</i>-<i>p</i>-toluoyl)-D-ribofuranosyl chloride, catalyzed with mercury(II) bromide, afforded 5-benzyl-2'-deoxy-3',5'-bis(<i>O</i>-<i>p</i>-toluoyl)uridine (<strong>22</strong>) and its α-anomer <strong>23</strong>. With Lawesson reagent, compound <strong>22</strong> gave 5-benzyl-4-thiouracil derivative <strong>24</strong> which was ammonolyzed to give 5-benzyl-2'-deoxycytidine (<strong>25</strong>). Analogously, compound <strong>23</strong> was converted into 5-benzyl-2-deoxy-α-cytidine (<strong>27</strong>). 5'-<i>O</i>-Benzoyl-5-benzyluridine (<strong>29</strong>) was converted into the 2,2'-anhydro derivative <strong>30</strong> which on reaction with hydrogen chloride afforded 3'-chloro-3'-deoxynucleoside <strong>31</strong>. This compound was reduced with tributylstannane and the obtained 2'-deoxynucleoside <strong>32</strong> on treatment with thionyl chloride gave a mixture of <i>erythro- </i>and <i>threo</i>-3'-chloro-2',3'-dideoxynucleosides (<strong>33</strong> and <strong>34</strong>, respectively) which were reduced to 5'-<i>O</i>-benzoyl-5-benzyl-2',3'-dideoxyuridine (<strong>35</strong>). Compound <strong>35</strong> reacted with Lawesson reagent under formation of 4-thiouracil derivative <strong>36</strong> and this was deblocked to 5-benzyl-4-thio-2',3'-dideoxyuridine (<strong>37</strong>). On heating with ammonia, compound <strong>37</strong> was converted into 5-benzyl-2',3'-dideoxycytidine (<strong>38</strong>). Reaction of 4-thiouracil derivative with methyl iodide and subsequent hydrazinolysis afforded 4-hydrazino derivative <strong>40</strong> which was heated with silver oxide in ethanol to give a mixture of anomeric 5-benzyl-1-(2,3-dideoxyribofuranosyl)-2(1<i>H</i>)-pyrimidinones (<strong>42</strong>).

Title:Preparation of 5-Benzyluracil and 5-Benzylcytosine Nucleosides as Potential Inhibitors of Uridine Phosphorylase
Creators:
Krečmerová, Marcela
Hřebabecký, Hubert
Holý, Antonín
Uncontrolled Keywords:Uridine phosphorylase, 5-Benzyluracil, Nucleosides, Pyrimidine
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. 627-644
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19960627UNSPECIFIED
ID Code:963
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) Preparation of 5-Benzyluracil and 5-Benzylcytosine Nucleosides as Potential Inhibitors of Uridine Phosphorylase. Collection of Czechoslovak Chemical Communications, 61 (4). pp. 627-644. ISSN 0010-0765

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