Abstract
The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama.
Highlights
[24,25,26,27,28,29,30,31,32,33,34,35,36,37,38], report poison frog alkaloids [24,25,26,27,28,29,30,31,32,33,34,35,36,37,38], we report the total synthesis of ent-cis-195A and cis-195A and cis-211A
[3 H]nicotine and [3 H]verapamil uptake by TR-BBB13 and TR-iBRB2 cells, respectively, by at least 29%. These results suggest that ent-cis-195A and cis-211A are recognized by the cationic drug transport systems at the BBB and inner blood–retinal barrier (BRB)
Partially inhibited α7-receptor-mediated currents by 38% and 31%, respectively, while both alkaloids at 10 μM showed negligible effects on α4β2-receptor-mediated currents (Figure 3C–F). Analysis of their structure–activity relationship suggested that the 6-hydroxy moiety of cis-211A and 6-epi-211A might contribute to the partial blockade of α76 of 16 nicotinic ACh receptors
Summary
The skin extracts of Neotropical poison frogs contain a variety of lipophilic alkaloids, and over 800 alkaloids have been isolated or detected to date [1]. Many of these alkaloids show remarkable biological activities on the nervous system such as nicotinic acetylcholine receptors [2,3]. As part of remains a program d no total synthesis of this alkaloid has been to reported, its absolute configuration unknown to date The synthesis of cis-211A enabled the determination of its absolu of cis-211A enabled the determination of its absolute configuration
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
