Z. Janeba, M. Masojídková, A. Holý
Mar 29, 2010
Citations
0
Influential Citations
4
Citations
Journal
Collection of Czechoslovak Chemical Communications
Abstract
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 .