Pyrrolovesamicols—Synthesis, structure and VAChT binding of two 4-fluorobenzoyl regioisomers

This Letter describes the synthesis of two regioisomers of a new class of vesamicol analogs as possible ligands for imaging the vesicular acetylcholine transporter in future PET studies. The two pyrrolovesamicols (±)-6a and (±)-6b were synthesized by nucleophilic ring opening reaction of a tetrahydroindole epoxide precursor with 4-phenylpiperidine. The reaction mechanism of the synthesis was studied by HPLC and the molecular structures were determined by X-ray structure analysis. Unexpected low binding affinities to VAChT (Ki = 312 ± 73 nM for (±)-6a and Ki = 7320 ± 1840 nM for (±)-6b) were determined by competitive binding analysis using a cell line stably transfected with ratVAChT and (−)-[3H]vesamicol.

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