Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(β-D-Hexofuranosyl)adenine

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Title:Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(β-D-Hexofuranosyl)adenine
Creators:
Hřebabecký, Hubert
Dočkal, Jan
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 59, 6, pp. 1408-1419

Abstract

<p>Condensation of 1,2-di-<i>O</i>-acetyl-3,5,6-tri-<i>O</i>-benzoyl-D-glucofuranose with <i>N</i><sup>6</sup>-benzoyladenine, catalyzed with tin tetrachloride, afforded nucleoside <i>I</i>. Partial deacetylation of <i>I</i>, followed by mesylation, gave 9-(3,5,6-tri-<i>O</i>-benzoyl-2-<i>O</i>-methanesulfonyl-β-D-glucofuranosyl)adenine (<i>III</i>). 9-(2,5,6-Tri-<i>O</i>-acetyl-3-<i>O</i>-methanesulfonyl-β-D-glucofuranosyl)-<i>N</i><sup>6</sup>-benzoyladenine (<i>IV</i>) was prepared by condensation of 1,2,5,6-tetra-<i>O</i>-acetyl-3-<i>O</i>-methanesulfonyl-D-glucofuranose with <i>N</i><sup>6</sup>-benzoyladenine. Reaction of mesyl derivative <i>III</i> with methanolic sodium methoxide and of mesyl derivative <i>IV</i> with methanolic ammonia led to 2',3'-anhydronucleosides <i>V</i> and <i>VI</i> which were acetylated to give the respective 9-(5,6-di-<i>O</i>-acetyl-2,3-anhydro-β-D-mannofuranosyl)adenine (<i>VII</i>) and 9-(5,6-di-<i>O</i>-acetyl-2,3-anhydro-β-D-allofuranosyl)adenine (<i>VIII</i>). Epoxy derivative <i>VII</i> was cleaved with bromotrimethylsilane, affording a mixture of 9-(5,6-di-<i>O</i>-acetyl-2-bromo-2-deoxy-β-D-glucofuranosyl)adenine (<i>Xa</i>) and 9-(5,6-di-<i>O</i>-acetyl-3-bromo-3-deoxy-β-D-altrofuranosyl)adenine (<i>XIa</i>), epoxy derivative <i>VIII</i> was cleaved analogously to give 9-(5,6-di-<i>O</i>-acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine (<i>XIIa</i>). Their dehalogenation with tributylstannane and subsequent deacetylation led to 9-(2-deoxy-β-D-<i>arabino</i>-hexofuranosyl)adenine (<i>Xc</i>), 9-(3-deoxy-β-D-<i>arabino</i>-hexofuranosyl)adenine (<i>XIc</i>) and 9-(3-deoxy-β-D-<i>ribo</i>-hexofuranosyl)adenine (<i>XIIc</i>). 9-(2,5,6-Tri-<i>O</i>-acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine (<i>XIId</i>), which was prepared by acetylation of <i>XIIa</i>, on reductive elimination with Cu/Zn couple and subsequent deacetylation gave 9-(2,3-dideoxy-β-D-<i>erythro</i>-hex-2-enofuranosyl)adenine (<i>XIV</i>). 9-(2,3-Dideoxy-β-D-<i>erythro</i>-hexofuranosyl)adenine (<i>XVI</i>) was obtained either by catalytic hydrogenation of bromo derivative <i>XIId</i> followed by deacetylation, or by catalytic hydrogenation of didehydro derivative <i>XIV</i>. The synthesized nucleosides were tested for antiviral activity.

Title:Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(β-D-Hexofuranosyl)adenine
Creators:
Hřebabecký, Hubert
Dočkal, Jan
Holý, Antonín
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:59
Number:6
Page Range:pp. 1408-1419
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19941408UNSPECIFIED
ID Code:562
Item Type:Article
Deposited On:06 Feb 2009 17:01
Last Modified:06 Feb 2009 16:02

Citation

Hřebabecký, Hubert; Dočkal, Jan; Holý, Antonín (1994) Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(β-D-Hexofuranosyl)adenine. Collection of Czechoslovak Chemical Communications, 59 (6). pp. 1408-1419. ISSN 0010-0765

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