New pyridine monoterpene alkaloids (PMTAs) have been synthesized from the iridoid glycosides 8-epi-loganin, cornin, and antirrinoside by treatment with beta-glucosidase and aqueous NH4-OAc. The PMTA from antirrinoside contained an 8-alpha-OAc group from the opened 7,8-epoxide moiety. Treatment of genipin, the aglycone of geniposide, with HCl(g) and NH3(g) yielded the PMTA racemigerine, a known plant isolate, in which the C=C-CH2OH side chain was converted to C=C-CH3. Reaction of geniposide with beta-glucosidase and aqueous NH4OAc led to oligomeric alkaloids, but at high dilution a dimer was obtained whose structure was formally that of a Diels-Alder adduct between racemigerine and a dihydropyridine. These biomimetic semisyntheses were analyzed in terms of reaction mechanisms and the relative paucity of known plant PMTAs in comparison with the multitudinous occurrence of their presumed iridoid glycoside precursors.

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).

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The iridoid glucoside antirrhinoside (1) was transformed into polysubstituted 3-azabicyclo[3.3.0]octanes 3, 12, and 13 in 4 to 5 steps. Ozonolysis of the diacetonide of 1 and of its 7-deoxy-derivative 8 afforded cyclopentanoids 2 and 10, respectively. Conditions for the selective conversion of 2 and 10 into the corresponding ditosylates 4 and 11 were investigated. Cyclization of 4 and 11 was achieved with benzylamine and 2-methoxybenzylamine to yield bicyclic pyrrolidines 3, 12, and 13. Additional building blocks 14 and 15 were obtained by selective deprotection of the N-benzyl and isopropylidene moieties in 12 and 13, respectively.

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