TY - JOUR
T1 - Synthesis of symmetrical and non-symmetrical bivalent neurotransmitter ligands
AU - Stuhr-Hansen, Nicolai
AU - Andersen, Jacob
AU - Thygesen, Mikkel Boas
AU - Strømgaard, Kristian
N1 - M1 - Copyright (C) 2017 American Chemical Society (ACS). All Rights Reserved.
CAPLUS AN 2016:1614242(Journal; Online Computer File)
PY - 2016/3
Y1 - 2016/3
N2 - 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.
AB - 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.
U2 - 10.1002/slct.201600116
DO - 10.1002/slct.201600116
M3 - Journal article
SN - 2365-6549
VL - 1
SP - 407
EP - 413
JO - ChemistrySelect
JF - ChemistrySelect
IS - 3
ER -