1-(3,5-O-Alkylidene-2-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracils

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Title:1-(3,5-O-Alkylidene-2-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracils
Creators:
Hřebabecký, Hubert
Buděšínský, Miloš
Masojídková, Milena
Havlas, Zdeněk
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 62, 6, pp. 957-970
Uncontrolled Keywords:Conformational analysis, Alkylidene derivatives, 4-<i>C</i>-Hydroxymethyluridine

Abstract

1-(2,3-<i>O</i>-Cyclohexylidene-4-<i>C</i>-hydroxymethyl-α-L-lyxofuranosyl)uracil (<strong>1</strong>) was converted in seven steps into 1-(2-deoxy-4-<i>C</i>-hydroxymethyl-α-L-<i>threo</i>-pentofuranosyl)uracil (<strong>8</strong>) and further into 1-(2-deoxy-4-<i>C</i>-hydroxymethyl-3,5-<i>O</i>-isopropylidene-α-L-<i>threo</i>-pentofuranosyl)uracil (<strong>9</strong>). Successive benzoylation, removal of the isopropylidene group, reaction with acetaldehyde diethyl acetal, and debenzoylation afforded (<i>R</i>)- and (<i>S</i>)-1-(2-deoxy-3,5-<i>O</i>-ethylidene-4-<i>C</i>-hydroxymethyl-α-L-<i>threo</i>-pentofuranosyl)uracil (<strong>10a</strong> and <strong>10b</strong>, respectively). Reaction of 1-(2-deoxy-4-<i>C</i>-triphenylmethyloxymethyl-α-L-<i>threo</i>-pentofuranosyl)uracil (<strong>14</strong>) with dichloromethane under conditions of phase transfer, followed by detritylation, afforded 1-(2-deoxy-4-<i>C</i>-hydroxymethyl-3,5-<i>O</i>-methylidene-α-L-<i>threo</i>- pentofuranosyl)uracil (<strong>15</strong>). Compound <strong>14</strong> was obtained from the derivative <strong>8</strong> by partial silylation, tritylation and desilylation. The absolute configuration of the isomeric ethylidene derivatives <strong>10a</strong> and <strong>10b</strong> was determined by NMR spectroscopy and the population of the deoxypentofuranose ring conformers was derived from the vicinal coupling constants <i>J</i>(H,H). The obtained results were compared with energy calculations. Neither of the prepared nucleoside analogues was active <i>in vitro</i> against HIV-1 and HIV-2.

Title:1-(3,5-O-Alkylidene-2-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracils
Creators:
Hřebabecký, Hubert
Buděšínský, Miloš
Masojídková, Milena
Havlas, Zdeněk
Holý, Antonín
Uncontrolled Keywords:Conformational analysis, Alkylidene derivatives, 4-<i>C</i>-Hydroxymethyluridine
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:6
Page Range:pp. 957-970
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19970957UNSPECIFIED
ID Code:1177
Item Type:Article
Deposited On:06 Feb 2009 17:07
Last Modified:06 Feb 2009 16:07

Citation

Hřebabecký, Hubert; Buděšínský, Miloš; Masojídková, Milena; Havlas, Zdeněk; Holý, Antonín (1997) 1-(3,5-O-Alkylidene-2-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracils. Collection of Czechoslovak Chemical Communications, 62 (6). pp. 957-970. ISSN 0010-0765

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