Preparation of Chloro and Sulfanyl Derivatives of 1-(2-Deoxy-4-C-hydroxymethyl-α-L-threo-Pentofuranosyl)uracil

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Title:Preparation of Chloro and Sulfanyl Derivatives of 1-(2-Deoxy-4-C-hydroxymethyl-α-L-threo-Pentofuranosyl)uracil
Creators:
Hřebabecký, Hubert
Balzarini, Jan
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 62, 7, pp. 1114-1127
Uncontrolled Keywords:Antivirals, 2'-Deoxy-4'-<i>C</i>-hydroxymethyluridine derivatives

Abstract

3'-Chloro and 3'-acetylsulfanyl derivatives of 1-(2-deoxy-4-<i>C</i>-hydroxymethyl-α-L-<i>threo</i>-pentofuranosyl)uracil were prepared by reaction of 2,3'-anhydro-1-{5'-<i>O</i>-benzoyl-4'-<i>C</i>-[(benzoyloxy)methyl]-2'-deoxy-α-L-<i>erythro</i>-pentofuranosyl}uracil (<strong>3</strong>) with hydrogen chloride and thioacetic acid, respectively. The reaction with hydrogen chloride gave a mixture of N-1 and N-3 substituted uracil derivatives <strong>12</strong> and <strong>14</strong>. Reaction of 1-{3-<i>O</i>-benzoyl-4-<i>C</i>-[(benzoyloxy)methyl]-2-deoxy-α-L-<i>threo</i>-pentofuranosyl}uracil (<strong>7</strong>) with thionyl chloride and subsequent debenzoylation afforded 1-(4-<i>C</i>-chloromethyl-2-deoxy-β-D-<i>erythro</i>-pentofuranosyl)uracil (<strong>19</strong>). Nucleophilic substitution with lithium thioacetate, followed by deacylation, converted 1-{3-<i>O</i>-benzoyl-4-<i>C</i>-[(benzoyloxy)methyl]-2-deoxy-5-<i>O</i>-<i>p</i>-toluenesulfonyl-α-L-<i>threo</i>-pentofuranosyl}uracil (<strong>9</strong>) into 1-(2-deoxy-4-<i>C</i>-sulfanylmethyl-β-D-<i>erythro</i>-pentofuranosyl)uracil (<strong>21</strong>). The obtained thiols were oxidized with iodine or air to give 1,1'-[disulfandiylbis(2,3-dideoxy-4-hydroxymethyl-α-L-threo-pentofuranose-3,1-diyl]di(pyrimidine-2,4-(1<i>H</i>,3<i>H</i>)-dione) (<strong>17</strong>) and 1,1'-[disulfandiylbis(2,5-dideoxy-4-hydroxymethyl-α-L-<i>threo</i>-pentofuranose-5,1-diyl]di(pyrimidine-2,4(1<i>H</i>,3<i>H</i>)-dione) (<strong>22</strong>). Reaction of 1-{3-acetylsulfanyl-5-<i>O</i>-methanesulfonyl-4-<i>C</i>-[(benzoyloxy)methyl]-2,3-dideoxy-α-L-<i>threo</i>-pentofuranosyl)}uracil (<strong>24</strong>) with methanolic sodium methoxide afforded 1-(3,5-anhydro-2,3-dideoxy-4-<i>C</i>-hydroxymethyl-3-sulfanyl-α-L-threo-pentofuranosyl)uracil (<strong>25</strong>). The same reagent was used in the preparation of 1-(3,5-anhydro-2-deoxy-4-<i>C</i>-hydroxymethyl-α-L-<i>threo</i>-pentofuranosyl)uracil (<strong>26</strong>) from 1-{4-<i>C</i>-[(benzoyloxy)methyl]-2-deoxy-5-<i>O</i>-<i>p</i>-toluenesulfonyl-α-L-<i>threo</i>-pentofuranosyl}uracil (<strong>8</strong>). From the series of 4'-substituted 2'-deoxyuridine derivatives, synthesized in this study, solely the 4'-chloromethyl derivative <strong>19</strong> and the oxetane derivative <strong>26</strong> exhibited an appreciable activity against HIV-1 and HIV-2.

Title:Preparation of Chloro and Sulfanyl Derivatives of 1-(2-Deoxy-4-C-hydroxymethyl-α-L-threo-Pentofuranosyl)uracil
Creators:
Hřebabecký, Hubert
Balzarini, Jan
Holý, Antonín
Uncontrolled Keywords:Antivirals, 2'-Deoxy-4'-<i>C</i>-hydroxymethyluridine derivatives
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. 1114-1127
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19971114UNSPECIFIED
ID Code:1191
Item Type:Article
Deposited On:06 Feb 2009 17:07
Last Modified:06 Feb 2009 16:07

Citation

Hřebabecký, Hubert; Balzarini, Jan; Holý, Antonín (1997) Preparation of Chloro and Sulfanyl Derivatives of 1-(2-Deoxy-4-C-hydroxymethyl-α-L-threo-Pentofuranosyl)uracil. Collection of Czechoslovak Chemical Communications, 62 (7). pp. 1114-1127. ISSN 0010-0765

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