Synthesis of N9- and N7-[2-Hydroxy-3-(phosphonomethoxy)propyl] Derivatives of N6-Substituted Adenines, 2,6-Diaminopurines and Related Compounds

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Title:Synthesis of N9- and N7-[2-Hydroxy-3-(phosphonomethoxy)propyl] Derivatives of N6-Substituted Adenines, 2,6-Diaminopurines and Related Compounds
Creators:
Krečmerová, Marcela
Masojídková, Milena
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 69, 10, pp. 1889-1913
Uncontrolled Keywords:Phosphonates, Oxirane ring opening, Nucleotides, Epoxides, Purines, Acyclic nucleotide analogues, Nucleosides, Antivirals, HPMPA

Abstract

Base-catalyzed reactions of diethyl [(oxiranylmethoxy)methyl]phosphonate (<strong>2</strong>) with purine bases (adenine, 2,6-diaminopurine, 6-chloropurine and 2-amino-6-chloropurine) gave corresponding 9- or 7-[2-hydroxy-3-(phosphonomethoxy)propyl] purines. The adenine and 2,6-diaminopurine derivatives cyclize to cyclic phosphonates <strong>4</strong> and <strong>6</strong>. The 9-[2-hydroxy-3-(phosphonomethoxy)propyl] derivatives of <i>N</i><sup>6</sup>-substituted adenine and 2,6-diaminopurine (<strong>15</strong>-<strong>27</strong>) were prepared by the treatment of diethyl {[3-(6-chloropurin-9-yl)-2-hydroxypropoxy]methyl}phosphonate (<strong>11</strong>) or diethyl {[3-(2-amino-6-chloropurin-9-yl)-2-hydroxypropoxy]methyl}phosphonate (<strong>13</strong>) with primary or secondary amines. The reaction of 6-chloro- or 2-amino-6-chloropurine derivatives (<strong>11</strong>, <strong>13</strong>) with thiourea gave the corresponding diethyl purine-6-thiol or 2-aminopurine-6-thiol phosphonates <strong>47</strong>, <strong>48</strong>. The guanine derivative <strong>49</strong> was prepared by the treatment of compound <strong>13</strong> with 80% acetic acid. All diethyl phosphonates were transformed to free phosphonic acids (<strong>31</strong>-<strong>43</strong>, <strong>50</strong>-<strong>52</strong>) by the action of bromotrimethylsilane and subsequent hydrolysis. <p>

Title:Synthesis of N9- and N7-[2-Hydroxy-3-(phosphonomethoxy)propyl] Derivatives of N6-Substituted Adenines, 2,6-Diaminopurines and Related Compounds
Creators:
Krečmerová, Marcela
Masojídková, Milena
Holý, Antonín
Uncontrolled Keywords:Phosphonates, Oxirane ring opening, Nucleotides, Epoxides, Purines, Acyclic nucleotide analogues, Nucleosides, Antivirals, HPMPA
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:69
Number:10
Page Range:pp. 1889-1913
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20041889UNSPECIFIED
ID Code:2311
Item Type:Article
Deposited On:06 Feb 2009 17:17
Last Modified:06 Feb 2009 16:17

Citation

Krečmerová, Marcela; Masojídková, Milena; Holý, Antonín (2004) Synthesis of N9- and N7-[2-Hydroxy-3-(phosphonomethoxy)propyl] Derivatives of N6-Substituted Adenines, 2,6-Diaminopurines and Related Compounds. Collection of Czechoslovak Chemical Communications, 69 (10). pp. 1889-1913. ISSN 0010-0765

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