Open AccessTaming Radical Pairs in the Crystalline Solid State: Discovery and Total Synthesis of Psychotriadine
Author(s) -
Jordan J. Dotson,
Ieva Liepuoniute,
James L Bachman,
Vince M. Hipwell,
Saeed I. Khan,
K. N. Houk,
Neil K. Garg,
Miguel A. Garcı́a-Garibay
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c01100
Subject(s) - chemistry , stereocenter , total synthesis , solid state , vicinal , stereochemistry , structural motif , molecule , combinatorial chemistry , organic chemistry , enantioselective synthesis , catalysis , biochemistry
Solid-state photodecarbonylation is an attractive but underutilized methodology to forge hindered C-C bonds in complex molecules. This study discloses the use of this reaction to assemble the vicinal quaternary stereocenter motif present in bis(cyclotryptamine) alkaloids. Our strategy was enabled by experimental and computational investigations of the role of substrate conformation on the success or failure of the solid-state photodecarbonylation reaction. This informed a crystal engineering strategy to optimize the key step of the total synthesis. Ultimately, this endeavor culminated in the successful synthesis of the bis(cyclotryptamine) alkaloid "psychotriadine," which features the elusive piperidinoindoline framework. Psychotriadine, a previously unknown compound, was identified in the extracts of the flower Psychotria colorata , suggesting it is a naturally occurring metabolite.