General Method of Preparation of N-[(S)-(3-Hydroxy-2-phosphonomethoxypropyl)] Derivatives of Heterocyclic Bases

[img]PDF - Authorized users only
Language: English
1048Kb
Title:General Method of Preparation of N-[(S)-(3-Hydroxy-2-phosphonomethoxypropyl)] Derivatives of Heterocyclic Bases
Creators:
Alexander, Petr
Holý, Antonín
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 58, 5, pp. 1151-1163

Abstract

Reaction of (<i>R</i>)-1-<i>O</i>-<i>p</i>-toluenesulfonyl-1,2,3-propanetriol (<i>IV</i>) with <i>N</i>-trimethylacetylimidazole (<i>II</i>) afforded (<i>R</i>)-1-<i>O</i>-<i>p</i>-toluenesulfonyl-3-<i>O</i>-trimethyacetyl-1,2,3-propanetriol (<i>V</i>) which was reacted with dimethoxymethane in the presence of phosphorus pentoxide to give (<i>R</i>)-2-<i>O</i>-methoxymethyl-1-<i>O</i>-<i>p</i>-toluenesulfonyl-3-<i>O</i>-trimethyacetyl-1,2,3-propanetriol (<i>VI</i>). Compound <i>VI</i> was treated with acetic anhydride and boron trifluoride etherate and the obtained 2-acetoxy derivative <i>VII</i> reacted with bromotrimethylsilane to give the intermediary bromomethyl ether <i>VIII</i>. Compound <i>VIII</i> on reaction with tris(2-propyl) phosphite afforded (<i>R</i>)-2-<i>O</i>-bis(2-propyl)phosphonomethyl-1-<i>O</i>-<i>p</i>-toluenesulfonyl-3-<i>O</i>-trimethyacetyl-1,2,3-propanetriol (<i>IX</i>). Condensation of synthon <i>IX</i> with sodium salts of adenine, 2,6-diaminopurine, or with cytosine, 6-azacytosine or 2-chloroadenine in the presence of cesium carbonate, afforded fully protected diesters <i>X</i> and <i>XIIIb</i> which on methanolysis and reaction with bromotrimethylsilane gave <i>N</i>-[(<i>S</i>)-(3-hydroxy-2-phosphonomethoxypropyl)] derivatives of adenine (<i>XIa</i>), 2- chloroadenine (<i>XIb</i>), 2,6-diaminopurine (<i>XIc</i>), cytosine (<i>XIVa</i>) and 6-azacytosine (<i>XIVb</i>). In an analogous reaction, sodium salt of 4-methoxy-2-pyrimidone reacted with compound <i>IX</i> to give an intermediate <i>XIIIa</i> which on treatment with methanolic ammonia and subsequent deblocking under the same conditions also afforded the cytosine derivative <i>XIVa</i>. Sodium salt of 2-amino-6-chloropurine was in this way converted into the corresponding 2-aminopurine derivative <i>XVIII</i>. Deprotection of this compound gave 9-(<i>S</i>)-(3-hydroxy-2-phosphonomethoxypropyl)-2-aminopurine (<i>XIX</i>).

Title:General Method of Preparation of N-[(S)-(3-Hydroxy-2-phosphonomethoxypropyl)] Derivatives of Heterocyclic Bases
Creators:
Alexander, Petr
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:58
Number:5
Page Range:pp. 1151-1163
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19931151UNSPECIFIED
ID Code:231
Item Type:Article
Deposited On:06 Feb 2009 16:59
Last Modified:06 Feb 2009 15:59

Citation

Alexander, Petr; Holý, Antonín (1993) General Method of Preparation of N-[(S)-(3-Hydroxy-2-phosphonomethoxypropyl)] Derivatives of Heterocyclic Bases. Collection of Czechoslovak Chemical Communications, 58 (5). pp. 1151-1163. ISSN 0010-0765

Repository Staff Only: item control page