N-methyldecahydroquinolines: an unexpected class of alkaloids from Amazonian poison frogs (Dendrobatidae)

Abstract

The dominant alkaloids previously identified in skin extracts of Amazonian dendrobatid frogs of the genus Ameerega are histrionicotoxins and 2,5-disubstituted decahydroquinolines. Analysis of alkaloids in skin extracts of Ameerega picta from Bolivia revealed that the alkaloid 257A, previously reported as a 2,5-disubstituted decahydroquinoline, is an N-methyl-2,5-disubstituted decahydroquinoline. We characterized alkaloids of another 12 of the more than 25 species recently assigned to the genus Ameerega, and five additional N-methyldecahydroquinolines were identified. In some cases, the relative configuration of the N-methyldecahydroquinolines was determined by comparison with the N-methylated products prepared from the corresponding 2,5-disubstituted decahydroquinolines of known relative configuration. A dietary source for N-methyldecahydroquinolines is unknown; however, myrmicine ants are the likely source for the 2,5-disubstituted decahydroquinolines. The alkaloids in skin extracts of three species of another genus of Amazonian poison frog, Adelphobates, were also characterized, but N-methyldecahydroquinolines were not detected.

Figure 1

Structures of N-methyldecahydroquinolines, decahydroquinolines, and a 5,6,8-trisubstituted indolizidine. The relative configurations of trans-233C, cis-257A, and trans-257A were established by comparison to the N-methyl derivatives of the corresponding decahydroquinolines. The relative configurations of the other alkaloids have not been established.

Figure 2

Mass spectrum and GC-FTIR spectrum of N-methyldecahydroquinoline trans-257A.