Synthesis of All Low-Energy Stereoisomers of the Tris(pyrrolidinoindoline) Alkaloid Hodgkinsine and Preliminary Assessment of Their Antinociceptive Activity
The previously unknown stereoisomers 3, 4, ent-1, and ent-4 of the tris(pyrrolidinoindoline) alkaloidshodgkinsine (1) and hodgkinsine B (2) were prepared by stereocontrolled total synthesis. In each synthesis,a catalyst-controlled intramolecular Heck reaction was the key step in appending a third cis-pyrrolidinoindoline ring to a hexacyclic chimonanthine precursor. Results of the preliminary evaluationof these hodgkinsine stereoisomers in the tail flick and capsaicin pain models are reported.