Synthesis of symmetrical and non-symmetrical bivalent neurotransmitter ligands

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Nicolai Stuhr-Hansen, Jacob Andersen, Mikkel Boas Thygesen, Kristian Strømgaard

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 methodol. establishes a facile route towards bivalent neurotransmitter ligands, and libraries of in total 40 sym. and non-sym. bivalent and monovalent dopamine and serotonin compds. linked through alkyl or PEG spacers of varying length were prepd. Interestingly, attempted synthesis of an O-tert-Bu analog 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. [on SciFinder(R)]
Original languageEnglish
JournalChemistrySelect
Volume1
Issue number3
Pages (from-to)407-413
Number of pages7
ISSN2365-6549
DOIs
Publication statusPublished - 2016

ID: 174370935