Synthesis of Novel Conformationally Locked Carbocyclic Nucleosides Derived from 5,5- and 6,6-Bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol

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Title:Synthesis of Novel Conformationally Locked Carbocyclic Nucleosides Derived from 5,5- and 6,6-Bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol
Creators:
Hřebabecký, Hubert
Masojídková, Milena
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 70, 4, pp. 519-538
Uncontrolled Keywords:Cyclic sulfates, Pyrimidines, Carbocyclic nucleosides, Purines, Nucleosides, Amines, Alkenes, Azides, Nucleobases, Azidohydroxylation, Antivirals

Abstract

(1<i>R</i>*,2<i>R</i>*,3<i>R</i>*,4<i>S</i>*)-3-Amino-6,6-bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol (<strong>13</strong>) was prepared from (bicyclo[2.2.1]hept-5-ene-2,2-diyl)dimethyl dibenzoate (<strong>7</strong>) via <i>cis</i>-diol <strong>8</strong>, cyclic sulfate <strong>10</strong>, and azide <strong>12</strong>. (1<i>R</i>*,2<i>R</i>*,3<i>S</i>*,4<i>S</i>*)-3-Amino-6,6-bis(hydroxymethyl)bicyclo[2.2.1]-heptan-2-ol (<strong>18</strong>) and (1<i>R</i>*,2<i>S</i>*,3<i>S</i>*,4<i>S</i>*)-3-amino-5,5-bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol (<strong>19</strong>) were obtained by addition of chromyl azide to double bond of <strong>7</strong>, chromatographic separation, debenzoylation and hydrogenation of resulting azides <strong>14</strong> and <strong>16</strong>. The amines <strong>13</strong>, <strong>18</strong>, and <strong>19</strong> were used to build (1<i>R</i>*,2<i>R</i>*,3<i>R</i>*,4<i>S</i>*)- (<strong>21a</strong>), (1<i>R</i>*,2<i>R</i>*,3<i>S</i>*,4<i>S</i>*)-3-(6-chloro-9<i>H</i>-purin-9-yl)-6,6-bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol (<strong>21b</strong>), and (1<i>R</i>*,2<i>S</i>*,3<i>S</i>*,4<i>S</i>*)-3-(6-chloro-9<i>H</i>-purin-9-yl)-5,5-bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol (<strong>21c</strong>), respectively. Ammonolysis of these compounds led to 6-amino-9<i>H</i>-purine derivatives <strong>22a</strong>-<strong>22c</strong>. 6-(Dimethylamino)-9<i>H</i>-purine analogues <strong>23a</strong>-<strong>23c</strong> and 6-(cyclopropylamino)-9<i>H</i>-purine analogues <strong>24a</strong>-<strong>24c</strong> were prepared by aminolysis of <strong>21a</strong>-<strong>21c</strong>. Reaction of amines <strong>13</strong>, <strong>18</strong>, and <strong>19</strong> with ethyl <i>N</i>-((2<i>E</i>)-3-ethoxymethacryloyl)carbamate afforded thymine derivatives <strong>28a</strong>-<strong>28c</strong>. <p>

Title:Synthesis of Novel Conformationally Locked Carbocyclic Nucleosides Derived from 5,5- and 6,6-Bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol
Creators:
Hřebabecký, Hubert
Masojídková, Milena
Holý, Antonín
Uncontrolled Keywords:Cyclic sulfates, Pyrimidines, Carbocyclic nucleosides, Purines, Nucleosides, Amines, Alkenes, Azides, Nucleobases, Azidohydroxylation, Antivirals
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:70
Number:4
Page Range:pp. 519-538
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20050519UNSPECIFIED
ID Code:2376
Item Type:Article
Deposited On:06 Feb 2009 17:18
Last Modified:06 Feb 2009 16:18

Citation

Hřebabecký, Hubert; Masojídková, Milena; Holý, Antonín (2005) Synthesis of Novel Conformationally Locked Carbocyclic Nucleosides Derived from 5,5- and 6,6-Bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol. Collection of Czechoslovak Chemical Communications, 70 (4). pp. 519-538. ISSN 0010-0765

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