Synthesis of a deuterium‐labelled standard of bufotenine (5‐HO‐DMT)

A synthetic route to deuterium-labeled bufotenine (5-HO-DMT) was developed using the Batcho–Leimgruber strategy. Starting from commercial 3-methyl-4-nitrophenol, the synthesis proceeded through benzyl protection and reaction with N,N-dimethylformamide–dimethylacetal. Reduction with Raney nickel and hydrazine hydrate gave an indole intermediate, which was then treated with oxalyl chloride, dimethylamine, and lithium aluminum [2H4]-hydride to introduce four deuterium atoms. Final hydrogenolysis removed the benzyl ether, yielding the labeled bufotenine. This method enables the preparation of a deuterated analog of the psychoactive compound for use in tracer studies or metabolic investigations.

Study at a glance

Abstract

Abstract The Batcho–Leimgruber strategy was employed to synthesize 3‐(2‐dimethylamino‐[ 2 H 4 ]‐ethyl)‐1 H ‐indol‐5‐ol (bufotenine, 5‐HO‐DMT) ( 8 ) from commercial 3‐methyl‐4‐nitro‐phenol ( 1 ), benzyl bromide and N,N –dimethylformamide–dimethylacetal. Compound 4 was synthesized from compound 3 using the Batcho–Leimgruber strategy in the presence of Raney nickel and hydrazine hydrate. Compound 4 was treated with oxalyl chloride, dimethylamine and lithium aluminum [ 2 H 4 ]‐hydride to yield [2‐(5‐benzyloxy‐1 H ‐indol‐3‐yl)‐[ 2 H 4 ]‐ethyl]‐dimethyl‐amine ( 7 ). The benzyl ether in compound 7 was cleaved by hydrogenolysis to give bufotenine 8 . Copyright © 2007 John Wiley & Sons, Ltd.