Abstract
Esters of cyclopropanecarboxylic acid demonstrate a substantial increase in stability under both acid- and base-catalyzed hydrolytic conditions. Comparison of the stability of valacyclovir 13 with the cyclopropane analogue 14 shows that at 40 degrees C and pH 6 the half-life of 14 is >300 h while the value for 13 is 69.7 h. CBS-QB3 calculations on isodesmic reactions for transfer of groups from an alkane to an ester show that a cyclopropyl group provides hyperconjugative stabilization.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Acyclovir / analogs & derivatives*
-
Acyclovir / chemistry
-
Acyclovir / pharmacology
-
Antiviral Agents / chemistry*
-
Antiviral Agents / pharmacology
-
Cyclopropanes / chemistry*
-
Cyclopropanes / pharmacology
-
Esters
-
Hydrolysis
-
Molecular Structure
-
Prodrugs / chemistry*
-
Prodrugs / pharmacology
-
Valacyclovir
-
Valine / analogs & derivatives*
-
Valine / chemistry
-
Valine / pharmacology
Substances
-
Antiviral Agents
-
Cyclopropanes
-
Esters
-
Prodrugs
-
cyclopropanecarboxylic acid
-
cyclopropane
-
Valine
-
Valacyclovir
-
Acyclovir