Gram-scale, chemoselective synthesis of N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC)

Noah A Setterholm; Frank E McDonald; Jeffrey H Boatright; P Michael Iuvone

doi:10.1016/j.tetlet.2015.01.167

Gram-scale, chemoselective synthesis of N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC)

Tetrahedron Lett. 2015 Jun 3;56(23):3413-3415. doi: 10.1016/j.tetlet.2015.01.167.

Authors

Noah A Setterholm¹, Frank E McDonald¹, Jeffrey H Boatright², P Michael Iuvone³

Affiliations

¹ Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, GA 30322 USA.
² Department of Ophthalmology, Emory University School of Medicine, 1365B Clifton Road NE, Atlanta, GA 30322 USA ; Rehabilitation R & D Center, Atlanta VA Medical Center, Decatur, GA USA 30033 USA.
³ Department of Ophthalmology, Emory University School of Medicine, 1365B Clifton Road NE, Atlanta, GA 30322 USA ; Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road NE, Atlanta, GA 30322 USA.

Abstract

N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC) is a potent activator of the TrkB receptor in mammalian neurons and of interest because of its potential therapeutic uses. In the absence of a commercial supply of HIOC, we sought to produce several grams of material. However, a synthesis of HIOC has never been published. Herein we report the preparation of HIOC by the chemoselective N-acylation of serotonin, without using blocking groups in the key acylation step.

Keywords: activation; amide; chemoselectivity; decarboxylation; kinase; serotonin; synthesis.

Abstract

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