Studies in the hydroxy-indole series

• Main Author: Attenburrow, John
• Published: University of Surrey 1950
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.751451

Owing to the interest shown in hydroxy indoles and especially in the theory put forward by Robinson that 6-hydroxy-tryptophane occurs naturally as a precursor of the harmala alkaloids, it was decided to attempt the preparation of 5- and 6-hydroxy tryptophanes. Reduction of 2-nitro-5- and 4-benzyIoxy-phenylpyruvic acids yielded 5- and 6-benzyloxy-indole-2-carboxylic acids which on hydrogenolyisis yielded the corresponding 5- and 6-hydroxy-indole-2-carboxylic acids. 5- and 6 -Bezyloxy-indoles were obtained by decarboxylation of the corresponding acids and on hydrogenolysis yielded 5- and 6-hydroxy indoles; these hydroxy-indoles were also obtained by decarboxylation of their corresponding carboxylic acids. 6-Benzyloxy-indole-3-aldehyde, ethyl 6-benzyloxy-indoIe-3-glyoxylate and ethyl 1-benzamido-2-(6-benzyloxy-indol-3'-yl)-acrylate were prepared from 6-benzyloxy-indole but were found to be impracticable as intermediates for the synthesis of 6-hydroxy-tryptophane. 5- and 6-Benzyloxy-3-dimethylamlnomethyl-indoles were prepared by the Mannich reaction on the respective indole ethers. The condensation of 5-benzyloxy-3-dimsthylaminomethy1-indole with diethyl acetamido-malonate gave a product from which no tractable products could be obtained. 6-Benzyloxy-3-dimethylaminomethyl-indole was condensed with diethyl acetamido-malonate to yield ethyl l-acetamido-l-carbethoxy-2-(6'-toenzyloxy- indol-3'-yl)-propionate which on hydrolysis and decarboxylation yielded acetyl-6-benzyloxy-tryptophane which was further hydrolysed to 6-benzyloxy-tryptophane. Careful hydrogenolysis of 6-benzyloxy-tryptophane and of its acetyl derivative yielded unstable products. it seems likely therefore that 6-hydroxy- tryptophane possesses so unstable a structure that its natural occurrence is unlikely.