Synthesis of Quaternary 1-[2-(Phosphonomethoxy)ethyl] Derivatives of 2,4-Diaminopyrimidine and Related Acyclic Nucleotide Analogs

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Title:Synthesis of Quaternary 1-[2-(Phosphonomethoxy)ethyl] Derivatives of 2,4-Diaminopyrimidine and Related Acyclic Nucleotide Analogs
Creators:
Holý, Antonín
Buděšínský, Miloš
Podlaha, Jaroslav
Císařová, Ivana
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 64, 2, pp. 242-256
Uncontrolled Keywords:NMR spectroscopy, <sup>1</sup>H and <sup>13</sup>C, PMEDAP, Phosphonates, Pyrimidines, Antivirals, Crystal structure, Acyclic nucleotide analogs

Abstract

Quaternization of 2,4-diaminopyrimidine (<strong>2</strong>) by diisopropyl 2-chloroethoxymethanephosphonate (<strong>3</strong>) followed by bromotrimethylsilane treatment and subsequent hydrolysis gave zwitterionic <i>N</i>1-[2-(phosphonomethoxy)ethyl] derivative, hydrogen {[2-(2,4-diaminopyrimidin-1-io)ethoxy]methyl}phosphonate (<strong>5</strong>). Its structure was confirmed by X-ray crystallography. The same product was obtained from 2-amino-4-[(dimethylaminomethylene)amino]pyrimidine (<strong>6</strong>) by an analogous reaction sequence followed by an aqueous ammonia treatment after the transsilylation reaction. Also the quaternizations of 4,6-diaminopyrimidine (<strong>7</strong>) and 2,4,6-triaminopyrimidine (<strong>8</strong>) with the halo derivative <strong>3</strong> afforded the zwitterionic <i>N</i>1-substituted compounds <strong>9</strong> and <strong>10</strong>, respectively. In contrast to this regiospecific reaction, 2-aminopyrimidine (<strong>11</strong>) gave on treatment with compound <strong>3</strong> and following deprotection the <i>exo</i>-<i>N</i>2-isomer <strong>13</strong>. This compound was also obtained by the reaction starting from 2-[(dimethylaminomethylene)amino]pyrimidine (<strong>12</strong>) which was prepared by treatment of compound <strong>11</strong> with dimethylformamide dineopentyl acetal. Also 2,3-diaminopyridine (<strong>14</strong>) gave by the above reaction a mixture of 2-amino-3-{[2-(phosphonomethoxy)ethyl]amino}pyridine (<strong>15</strong>) and quaternary <i>N</i>1-[2-(phosphonomethoxy)ethyl] derivative (<strong>16</strong>). None of these analogs of the antiviral PMEDAP exhibited any antiviral activity against DNA viruses or retroviruses, nor any cytostatic activity. <p>

Title:Synthesis of Quaternary 1-[2-(Phosphonomethoxy)ethyl] Derivatives of 2,4-Diaminopyrimidine and Related Acyclic Nucleotide Analogs
Creators:
Holý, Antonín
Buděšínský, Miloš
Podlaha, Jaroslav
Císařová, Ivana
Uncontrolled Keywords:NMR spectroscopy, <sup>1</sup>H and <sup>13</sup>C, PMEDAP, Phosphonates, Pyrimidines, Antivirals, Crystal structure, Acyclic nucleotide analogs
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:64
Number:2
Page Range:pp. 242-256
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19990242UNSPECIFIED
ID Code:1473
Item Type:Article
Deposited On:06 Feb 2009 17:09
Last Modified:06 Feb 2009 16:09

Citation

Holý, Antonín; Buděšínský, Miloš; Podlaha, Jaroslav; Císařová, Ivana (1999) Synthesis of Quaternary 1-[2-(Phosphonomethoxy)ethyl] Derivatives of 2,4-Diaminopyrimidine and Related Acyclic Nucleotide Analogs. Collection of Czechoslovak Chemical Communications, 64 (2). pp. 242-256. ISSN 0010-0765

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