The synthesis of tricyclic cocaine analogs via the 1,3-dipolar cycloaddition of oxidopyridinium betaines

Article abstract of DOI:10.1016/S0040-4039(97)10524-X

Tricyclic cocaine analogs with a spatially fixed nitrogen lone pair were synthesized as structural probes of the dopamine transporter. A tandem cycloaddition/radical cyclization protocol was used to gain access to analog 12 with a two carbon linker between C-2 and N-8. On the other hand, the intramolecular dipolar cycloaddition reaction of betaine 13 was used to procure cocaine analog 18 and its C-3 epimer 19 in which an extra ring links N-8 to C-6. Binding studies reveal 12c and 18 to be potent DAT ligands.