Synthesis of Racemic and Enantiopure Forms of β-Carboline Alkaloid Brevicolline

Dedicated to the memory of the late Professor Ferenc Fülöp (1952–2021)

Abstract

A new total synthesis of the pharmacologically active β-carboline alkaloid brevicolline is described. The new synthetic approach is based on a commercially available and inexpensive starting material and reagents leading to a practical synthesis of the racemic target molecule, the natural (S)-enantiomer, and its antipode. Initially, the construction of the β-carboline skeleton and functionalization at the C(4) position have been accomplished. The formation of dihydropyrrole structural unit was obtained as the result of an Au-catalyzed hydroamination reaction, which was followed by a reduction that led to the chiral intermediate. The synthetic route described here is developed to ensure the sustainable access of the racemic brevicolline in 11 steps with improved 48% overall yield compared to the previously reported methods.

Key words

brevicolline - natural product - β-carboline - total synthesis - chiral chromatography

Publication History

Received: 27 November 2021

Accepted after revision: 03 January 2022

Article published online:
15 February 2022

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