Bidirectional synthesis of montamine analogs

Fischer indole synthesis applied to the total synthesis of natural products

“…Montamine has a unique dimeric N,N 0 -diacyl hydrazide In 2015, Xu and co-workers described the total synthesis of alkaloid natural product montamine analogue 175 in 55% yield. 124 As depicted in Scheme 36, this group provided 3-(2hydroxyethyl)-5-methoxyindole (usually found as 5-methoxytryptophol, 176) through the FIS with p-methoxyphenylhydrazine hydrochloride 39 and 2,3-dihydrofuran 73. Whereas the yield of this treatment was modest, it nevertheless gave a reasonable, one-step method to an indole suitably substituted having an oxygen group at the 5-position and ethyl alcohol scaffold at the 3-position.…”

“…Alcohol 176 gave the advanced montaine analogue 175 in several steps (Scheme 36). 124 The monoterpene indole alkaloids are an extremely different group of naturally occurring compounds, which were provided in a widespread series of medicinal plants. They have natural structural complication and a number of signicant biological properties, which qualies a gure of them to be principle candidates for anti-arrhythmic, anti-malarial and anti-cancer agents.…”

Total synthesis of putative montamine and a proposed structural reassignment

“…Purification by flash chromatography eluting with hexanes-ethyl acetate (1 : 3) gave the title compound as a yellow solid (18. 5…”

“…Both of our research groups have an ongoing interest in this natural product, separately reporting similar synthetic routes to the bis(indolyl)ethylhydrazine core 4 and montamine dimethyl ether, 5 respectively. Using the bidirectional approach in the latter example as a guide, 5 two planned syntheses of 1 are shown in Scheme 1.…”

“…Both of our research groups have an ongoing interest in this natural product, separately reporting similar synthetic routes to the bis(indolyl)ethylhydrazine core 4 and montamine dimethyl ether, 5 respectively. Using the bidirectional approach in the latter example as a guide, 5 two planned syntheses of 1 are shown in Scheme 1. It was envisaged montamine (1) could be obtained by the selective deprotection of either its diisopropyl ether 3 or dibenzyl ether 4 which are both available from the hydrazines 5 and 6 by diacylation with the feruloyl chloride 7 followed by deacetylation-detosylation.…”