ALTERNATIVE SYNTHESIS OF 9-{3-[(DIISOPROPOXYPHOSPHORYL)METHOXY]-2-HYDROXYPROPYL}ADENINE AND ITS FREE PHOSPHONATES SUBSTITUTED AT THE C-8 POSITION OF PURINE BASE

被引：4

作者：

Janeba, Zlatko ^{[1
]}

Masojidkova, Milena ^{[1
]}

Holy, Antonin ^{[1
]}

机构：

[1] Acad Sci Czech Republ, Inst Organ Chem & Biochem, Vvi, CR-16610 Prague 6, Czech Republic

来源：

COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS | 2010年 / 75卷 / 03期

关键词：

Acyclic nucleoside phosphonates; Acyclic nucleotide analogues; HPMPA; Alkylation; Nucleophilic substitution; Intramolecular cyclization; ACYCLIC NUCLEOSIDE PHOSPHONATES; NUCLEOTIDE ANALOGS; DNA VIRUS; INTRAVITREAL CIDOFOVIR; ANTIVIRAL ACTIVITY; HPMPC CIDOFOVIR; PMEA ADEFOVIR; DERIVATIVES; (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE; CHEMOTHERAPY;

D O I：

10.1135/cccc2009569

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

For its high therapeutic effect, (S)-9-[3-hydroxy-2-(phosphonomethoxy) propyl]adenine (HPMPA) is an important member of a class of acyclic nucleoside phosphonates (ANPs). Although its constitutional isomer, 9-[2-hydroxy-3-(phosphonomethoxy) propyl]adenine (iso-HPMPA), exhibits no antiviral activity, our general interest in C-8 substituted adenine ANPs led us to prepare certain iso-HPMPA derivatives modified at the C-8 position of adenine. Novel alkylating agent, diisopropyl {[2-(tetrahydro-2-pyranyl)oxy-3-tosyloxypropoxy]methyl} phosphonate (9), was prepared by procedure starting from allyl alcohol (4). 9-{3-[(Diisopropoxyphosphoryl)methoxy]-2-hydroxypropyl}adenine (12) was prepared by alkylation of adenine with the alkylating agent 9 followed by acid hydrolysis, although elimination by-product 9-{3-[(diisopropoxyphosphoryl)methoxy]prop-1-enyl}adenine (11) predominated in the reaction mixture. Bromination of the compound 12 gave 8-bromoadenine derivative 13 quantitatively. Nucleophilic substitutions of the bromine atom of compound 13 with N- and O-nucleophiles, followed by phosphonate deprotection, afforded the free phoshonic acids 15-18.

引用

页码：371 / 381

页数：11

共 16 条

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