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

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. Copyright © 1992 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim