A transition-metal-catalyzed cyclopropanation followed by ring opening was investigated for the synthesis of octahydroquinolines 4 and decahydroquinolines 5 having a quaternary carbon center at the angular position, which are core structures of the fawcettimine-type alkaloids. A tandem reaction was also established for the synthesis of decahydroquinolines 5 and the tricyclic compound 6 through an iminium ion intermediate, readily produced by acidic treatment of cyclopropane 2.

AbstractValuable synthetic routes to the Lycopodium alkaloid lycodine (1) and its unsymmetric dimers, complanadines A (4) and B (5), have been developed. Regioselective construction of the bicyclo[3.3.1]nonane core structure of lycodine was achieved by a remote functionality-controlled Diels–Alder reaction and subsequent intramolecular Mizoroki–Heck reaction. A key coupling reaction of the lycodine units, pyridine N-oxide (66) and aryl bromide (65), through C−H arylation at the C1 position of 66 provided the unsymmetric dimer structure at a late stage of the synthesis. This strategy greatly simplified the construction of the dimeric architecture and functionalization. Complanadines A (4) and B (5) were synthesized by adjusting the oxidation level of the bipyridine mono-N-oxide (67). The diverse utility of this common intermediate (67) suggests a possible biosynthetic pathway of complanadines in Nature. Both enantiomers of lycodine (1) and complanadines A (4) and B (5) were prepared in sufficient quantities for biological evaluation. The effect on neuron differentiation of PC-12 cells upon treatment with culture medium, in which human astrocytoma cells had been cultured in the presence of 1, 4, or 5 was evaluated.

Alkaloid Synthesis Structurally complex Lycopodium alkaloid complanadines A and B, both with unsymmetrical dimer architectures, were effectively synthesized by designing an appropriate intermediate based on C−H arylation. Our result suggests the intermediacy of a mono-N-oxide in the biosynthesis of dimeric alkaloids. This competent route enabled the evaluation of neuronal differentiation effects of both natural-type enantiomers and antipodes. More information can be found in the Full Paper by C. Tsukano et al. on page 802 ff.