Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(4-C-Hydroxymethyl-α-L-pentofuranosyl)adenine

[img]PDF - Authorized users only
Language: English
156Kb
Title:Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(4-C-Hydroxymethyl-α-L-pentofuranosyl)adenine
Creators:
Hřebabecký, Hubert
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 59, 7, pp. 1654-1664

Abstract

<p>Condensation of 1,2-di-<i>O</i>-acetyl-3,5-di-<i>O</i>-benzoyl-4-<i>C</i>-benzoyloxymethyl-L-arabinofuranose with <i>N</i><sup>6</sup>-benzoyladenine, catalyzed with tin tetrachloride, afforded nucleoside <i>I</i>, which upon partial deacetylation and subsequent mesylation was converted into 9-(3,5-di-<i>O</i>-benzoyl-4-<i>C</i>-benzoyloxymethyl-2-<i>O</i>-methanesulfonyl-α-L-arabinofuranosyl)adenine (<i>III</i>). 9-(2,5,6-Tri-<i>O</i>-acetyl-4-<i>C</i>-acetoxymethyl-3-<i>O</i>-methanesulfonyl-α-L-arabinofuranosyl)-<i>N</i><sup>6</sup>-benzoyladenine (<i>V</i>) was obtained by condensation of 1,2,5-tri-<i>O</i>-acetyl-4-<i>C</i>-acetoxymethyl-3-<i>O</i>-methanesulfonyl-L-arabinose with <i>N</i><sup>6</sup>-benzoyladenine. Reaction of mesyl derivatives <i>III</i> and <i>V</i> with methanolic sodium methoxide afforded 2',3'-anhydro nucleosides <i>VIa</i> and <i>VIIa</i>, which were acetylated to give 9-(5-<i>O</i>-acetyl-4-<i>C</i>-acetoxymethyl-2,3-anhydro-α-L-ribofuranosyl)adenine (<i>VIb</i>) and 9-(5-<i>O</i>-acetyl-4-<i>C</i>-acetoxymethyl-2,3-anhydro-α-L-lyxofuranosyl)adenine (<i>VIIb</i>). Epoxy derivative <i>VIb</i> was cleaved with bromotrimethylsilane to 9-(5-<i>O</i>-acetyl-4-<i>C</i>-acetoxymethyl-2-bromo-2-deoxy-α-L-arabinofuranosyl)adenine (<i>VIIIa</i>); the same reaction with epoxy derivative <i>VIIb</i> afforded a mixture of 9-(5-<i>O</i>-acetyl-4-<i>C</i>-acetoxymethyl- 2-bromo-2-deoxy-α-L-xylofuranosyl)adenine (<i>IXa</i>) and 9-(5-<i>O</i>-acetyl-4-<i>C</i>-acetoxymethyl-3-bromo- 3-deoxy-α-L-arabinofuranosyl)adenine (<i>Xa</i>). Their dehalogenation with tributylstannane and subsequent deacetylation led to 9-(2-deoxy-4-<i>C</i>-hydroxymethyl-α-L-<i>erythro</i>-pentofuranosyl)adenine (<i>VIIIc</i>), 9-(2-deoxy-4-<i>C</i>-hydroxymethyl- α-L-<i>threo</i>-pentofuranosyl)adenine (<i>IXc</i>) and 9-(3-deoxy-4-<i>C</i>-hydroxymethyl-α-L-<i>threo</i>-pentofuranosyl)adenine (<i>Xc</i>). 9-(2,5-Di-<i>O</i>-acetyl-4-<i>C</i>-acetoxymethyl-2-bromo-2-deoxy-α-L-arabinofuranosyl)adenine (<i>VIIId</i>), prepared by acetylation of <i>VIIIa</i>, on reductive elimination with Cu/Zn couple and subsequent deacetylation afforded 9-(2,3-dideoxy-4-<i>C</i>-hydroxymethyl-α-L-<i>glycero</i>-pent-2-enofuranosyl)adenine (<i>XIb</i>). 9-(2,3-Dideoxy-4-<i>C</i>-hydroxymethyl-α-L-<i>glycero</i>-pentofuranosyl)adenine (<i>XIIb</i>) was obtained either by catalytic hydrogenation of bromo derivative <i>VIIId</i>, followed by deacetylation, or by catalytic hydrogenation of didehydro derivative <i>XIb</i>. The nucleosides synthesized were tested for antiviral activity.

Title:Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(4-C-Hydroxymethyl-α-L-pentofuranosyl)adenine
Creators:
Hřebabecký, Hubert
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:7
Page Range:pp. 1654-1664
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19941654UNSPECIFIED
ID Code:588
Item Type:Article
Deposited On:06 Feb 2009 17:02
Last Modified:06 Feb 2009 16:02

Citation

Hřebabecký, Hubert; Holý, Antonín (1994) Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(4-C-Hydroxymethyl-α-L-pentofuranosyl)adenine. Collection of Czechoslovak Chemical Communications, 59 (7). pp. 1654-1664. ISSN 0010-0765

Repository Staff Only: item control page