2.5- Disubstituted decahydroquinoline

SAM, samandarines BTX, batrachotoxins HTX, histrionicotoxins PTX, pumiliotoxins aPTX, allopumiliotoxins hPTX, homopumiliotoxins DHQ, 2,5-disubstituted decahydroquinolines 3,5-P, 3,5-d [substituted pyrrolizidines 3,5-1 and 5,8-1, disubstituted indolizidines 1,4-Q, 1,4-disubstituted quinolizidines Epi, epibatidine Pseudophry, pseudophrynamines. With the exception of 3,5-P and 3,5-1, these alkaloids are not known to occur in arthropods (see text). Histrionicotoxins may occur in Minyobates and Mantella, but the evidence is not conclusive. 

The neotropical dart poison frogs contain a remarkable diversity of alkaloids, and the 2,5-disubstituted decahydroquinolines represent, a major class of these amphibian alkaloids[21]. Isolation of these alkaloids from some ants strengthens a dietary hypothesis for the origin of the above alkaloids that have been detected in extracts of frog skin[22]. In addition, these alkaloids containing both cis and trans ring fusion have been identified as well as diastereomers at the C-2 and C-5 position. 

Simple 2,5-disubstituted decahydroquinolines do not appear to have been reported to occur in Nature except in certain amphibians. Decahydroquinolines, like histrionicotoxins, occur in a range of dendrobatid frogs. These two classes of dendrobatid alkaloids often occur together in the same species or population. Indeed, the 19-carbon decahydroquinoline 269AB (or 269A and 269B) always appears to accompany the 19-carbon... 

In an effort to identify possible sources of the 16 alkaloids found in the skin of the Panamanian poison frog Dendrobates auratus, ants from a total of 61 terrestrial nests were analyzed [124]. The alate queens of one species of myr-micine ants (Solenopsis (Diplorhoptrum) sp.) collected at Cerro Ancon were found to contain the decahydroquinoline (-)-ds-195A (112) which was also present as a minor alkaloid in the skin of the microsympatric population of D. auratus. Moreover, from wingless ants of two nests collected at Isla Taboga and identified as Megalomyrmex silvestrU the same workers isolated the stereo-isomeric 3,5-disubstituted pyrrolizidines rfs-251 K (117) and trans-251 K (118) in the same ratio 3 1 that was present in the skin of a microsympatric population of D. auratus (Fig. 20) [124]. 

A series of studies have been reported on the basicities and nucleo-philicities of 4-substituted and 4,4 -disubstituted piperidines, together with related work on decahydroquinolines.211-215 Substituent effects on pKa values determined in methanol of 4,4 -disubstituted A-methyl-piperidines216,217 and 1,2,5-trimethylpiperidines (25)218 were found to be dependent on o i.e., as expected, resonance effects are absent, the hydroxyl substituent where present taking the axial conformation (24),216 owing to a bridging molecule of methanol. 

The monocyclic 2,6-disubstituted piperidines have been considered as possible precursors for dendrobatid alkaloids containing piperidine rings, such as the histrionicotoxins, decahydroquinolines, and gephyrotoxins (see Ref. J). Similarly, the monocyclic 2,5-disubstituted pyrrolidines have been considered as possible precursors for dendrobatid alkaloids containing pyrrolidine rings, such as the pumiliotoxins, the indolizidines, and now the pyrrolizidines (see Ref. 5). It should be noted that 2,6-disubstituted piperidines and 2,5-disubstituted pyrrolidines occur only rarely in dendrobatid frogs, while in ants they appear as major venom constituents, along with pyrrolizidines and indolizidines. It has been proposed that the monocyclic piperidines and pyrrolidines may serve as biosynthetic precursors of the bicyclic alkaloids in ants 125,134). 

In 2008, Blechert et al. reported the total synthesis of e/jt-lepadin F (89) and G (90) by a tandem ene-yne-ene RCM [74]. Lepadins are members of marine alkaloids with decahydroquinoline framework. As a key step in their synthesis (Fig. 26) they planned to construct the decahydroquinoline core skeleton by a selective tandem ene-yne-ene RCM of the dienyne precursor (91). Craiceivably, two different reaction pathways could be expected (1) initiation of metathesis may occur at the terminal double bond followed by two consecutive RCMs to afford the desired 6/6 bicycle (92) or (2) initiation may occur on the disubstituted alkene followed by tandem RCMs to produce the undesired 5/7 bicycle (93). Considering the preference of initiation on monosubstituted double bond as well as the directing effect of free hydroxyl group, pathway (1) may be more favored. Gratilyingly, treatment of dienyne (91) with 10 mol% Gmbbs I catalyst smoothly provided the desired 6/6 bicycle (92) in 90% yield. 

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