Synthesis of Monoterpene Piperidines from the Iridoid Glucoside Antirrhinoside

Synthesis of five novel piperidine monoterpene alkaloids ( 17 − 21 ) using the iridoid glucoside antirrhinoside ( 4 ) as a synthon is described. Two strategies for their preparation were investigated: the first possible pathway involved an intermediate diol, 13, from which the piperidine ring was expected to be constructed via reaction of its ditosylate with an amine; the second strategy involved a double reductive amination as the key step to the piperidine ring, which proved successful. The stereochemistry of C-5 and C-9 in the obtained piperidine monoterpenes was the same as that reported for α-skytanthine ( 3 ), a known isolate from Skytanthus acutus (Apocynaceae).