Preparation of 7-hydroxy-2-oxoindolin-3-ylacetic acid and its [13C2], [5-n-3H], and [5-n-3H]-7-O-glucosyl analogues for use in the study of indol-3-yl-acetic acid catabolism

Abstract

An improved synthesis of 7-hydroxy-2-oxoindolin-3-ylacetic acid (14)via the base-induced condensation reaction between oxalate esters and 7-benzyloxyindolin-2-one is described. 7-Benzyloxyindolin-2-one was prepared in four steps and 50% overall yield from 3-hydroxy-2-nitrotoluene. The yield of the title compound (14) from 7-benzyloxyindolin-2-one was 56%. This route was used to prepare 7-hydroxy-2-oxoindolin-3-yl[¹³C₂]acetic acid (15) in 30% yield from [¹³C₂]oxalic acid dihydrate. The method could not be extended to the preparation, of the corresponding [¹⁴C₂]compound. However, an enzyme preparation from Zea mays roots catalysed the conversion of carrier-free [5-n-³H]indol-3-ylacetic acid with a specific activity of 16.7 Ci mmol^–1 to a mixture of 7-hydroxy-2-oxo[5-n-³H]indolin-3-ylacetic acid (16) and its [5-n-³H]-7-O-glucoside (18) in ca. 3 and 40% radiochemical yield respectively. The glucoside (18) was converted into the 7-hydroxy compound (16) in 80% yield by means of β-glucosidase.