Inhibitors of Phenylalanine Ammonia‐Lyase: 2‐Aminoindan‐2‐phosphonic Acid and Related Compounds

Abstract

Abstract 2‐Aminoindan‐2‐phosphonic acid ( 3 ) was synthesized for the first time both directly from 2‐indanone ( 7 ) as well as by alkylation of ethyl diethoxyphosphorylacetate with 1,2‐bis(bromomethyl)benzene ( 9 ) via 10 – 12 , respectively. 2‐Hydroxyindan‐2‐phosphonic acid ( 5 ) was obtained also from 7 via its diisopropyl ester 8 . Compound 3 was found to be a potent inhibitor of the plant enzyme phenylalanine ammonia‐lyase (EC 4.3.1.5) both in vitro and in vivo. Of the related 2‐aminoindan‐2‐carboxylic acid ( 4 ), compound 5 , and 1‐aminocyclopentylphosphonic acid ( 6 ), only 4 inhibited the enzyme but was far less inhibitory than 3 .