Article

Synthesis of Symmetrical and Non‐Symmetrical Bivalent Neurotransmitter Ligands

ChemistrySelect, Wiley, ISSN 2365-6549

Volume 1, 3, 2016

DOI:10.1002/slct.201600116, Dimensions: pub.1041245067,

Affiliations

Organisations

  1. (1) University of Copenhagen, grid.5254.6, KU

Countries

Denmark

Continents

Europe

Description

A novel procedure for synthesis of bivalent neurotransmitter ligands was developed by reacting O-benzyl protected N-nosylated dopamine and serotonin with alkyl- or PEG-linked diols under Fukuyama-Mitsunobu conditions in the presence of DIAD/PPh3 generating three different bivalent neurotransmitter ligands in a one-pot reaction. The methodology establishes a facile route towards bivalent neurotransmitter ligands, and libraries of in total 40 symmetrical and non-symmetrical bivalent and monovalent dopamine and serotonin compounds linked through alkyl or PEG spacers of varying length were prepared. Interestingly, attempted synthesis of an O-tert-butyl analogue of the N-nosylated serotonin precursor resulted in unexpected tert-butylations at the 1-, 2- and 6-positions of the indole skeleton. We found that upscaling of selected bivalent serotonin ligands was most efficiently performed via N,O-bis-nosyl-serotonin since global de-nosylation was carried out as a final step after Fukuyama-Mitsunobu dimerization.

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University of Copenhagen

Danish Open Access Indicator

2016: Unused

Research area: Medicine

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Times Cited: 1

Field Citation Ratio (FCR): 0.18