Under
superacidic conditions, aniline and indole derivatives are
sulfonylated at low temperature with easy-to-access arenesulfonic
acids or arenesulfonyl hydrazides. By modification of the functional-group
directing effect through protonation, this method allows nonclassical
site functionalization by overcoming the innate regioselectivity of
electrophilic aromatic substitution. This superacid-mediated sulfonylation
of arenes is complementary to existing methods and can be applied,
through protection by protonation, to the late-stage site-selective
functionalization of natural alkaloids and active pharmaceutical ingredients.
Positron emission tomography (PET) imaging of the myelin
sheath
is a powerful tool to investigate multiple sclerosis, monitor its
evolution, and support drug development. Radiotracers based on N,N-dimethylaminostilbene (MeDAS) fluorinated analogs have
been designed for myelin PET imaging but were never translated to
humans. We have synthesized three original fluorinated analogs of
MeDAS with low metabolic rates for which binding to myelin in a healthy
rat brain was demonstrated by fluorescence microscopy. A tosyl precursor
was synthesized for the lead compound PEGMeDAS and automated fluorine-18
radiolabeling afforded [18F]PEGMeDAS in 25 ± 5% radiochemical
yield and 102 ± 15 GBq/μmol molar activity. Biodistribution
in healthy rats demonstrated the brain penetration with low penetration
of radiometabolites. However, E to Z isomerization observed in plasma hampers further investigations
of this family of molecules and requires complementary data on the in vivo behavior of the Z isomer.
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