Synthesis of N-(3-Fluoro-2-phosphonomethoxypropyl) (FPMP) Derivatives of Heterocyclic Bases

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Title:Synthesis of N-(3-Fluoro-2-phosphonomethoxypropyl) (FPMP) Derivatives of Heterocyclic Bases
Creators:
Jindřich, Jindřich
Holý, Antonín
Dvořáková, Hana
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 58, 7, pp. 1645-1667

Abstract

A new group of compounds has been prepared: <i>N</i>-(3-fluoro-2-phosphonomethoxypropyl) (FPMP) derivatives of purine and pyrimidine bases which exhibit a significant selective activity against a broad spectrum of retroviruses. Racemic <i>N</i>-(3-fluoro-2-phosphonomethoxypropyl) derivatives of adenin (<i>V</i>), guanine (<i>IX</i>), cytosine (<i>XIII</i>), 2,6-diaminopurine (<i>XXI</i>), 3-deazaadenin e(<i>XVII</i>), xanthine (<i>X</i>) and hypoxanthin (<i>VI</i>) were prepared from the corresponding <i>N</i>-(3-fluoro-2-hydroxypropyl) derivatives after protection of amino group at the heterocyclic ring by selective benzoylation, reaction with diisopropyl <i>p</i>-toluenesulfonyloxymethylphosphonate (<i>II</i>), and subsequent removal of the protecting groups. Chiral FPMP derivatives were prepared by reaction of heterocyclic base with the corresponding chiral synthon (<i>XXX, XXXVII</i>) followed by deprotection. The required chiral synthons were obtained from enantiomeric 3-fluoro-1,2-propanediols by two methods. In the first, the primary hydroxyl group was tritylated, the obtained derivative was reacted with compound <i>II</i>, the trityl group was removed and the product was mesylated to give synthon <i>XXXVII</i>. The second pathway consisted in selective tosylation of the primary hydroxyl group and conversion of the secondary hydroxyl into the acetoxymethyl ether via the methoxymethyl ether; treatment of the acetoxy compound with bromotrimethylsilane and triisopropyl phosphite afforded the desired synthon <i>XXX</i>.

Title:Synthesis of N-(3-Fluoro-2-phosphonomethoxypropyl) (FPMP) Derivatives of Heterocyclic Bases
Creators:
Jindřich, Jindřich
Holý, Antonín
Dvořáková, Hana
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:7
Page Range:pp. 1645-1667
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19931645UNSPECIFIED
ID Code:283
Item Type:Article
Deposited On:06 Feb 2009 16:59
Last Modified:06 Feb 2009 15:59

Citation

Jindřich, Jindřich; Holý, Antonín; Dvořáková, Hana (1993) Synthesis of N-(3-Fluoro-2-phosphonomethoxypropyl) (FPMP) Derivatives of Heterocyclic Bases. Collection of Czechoslovak Chemical Communications, 58 (7). pp. 1645-1667. ISSN 0010-0765

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