BACKGROUND Prior work from these laboratories has centred on the development of enaminones as versatile intermediates for the synthesis of alkaloids and other nitrogen-containing heterocycles. In this paper we describe the enantioselective synthesis of indolizidine and quinolizidine analogues of bicyclic amphibian alkaloids via pyrrolidinylidene- and piperidinylidene-containing enaminones. RE...

Dienes embedded in quinolizidine and indolizidine structures can be prepared in four steps from cyclic nitrones and bicyclopropylidene. The key intermediates α-spirocyclopropanated N-heterocyclic ketones, generated via a domino 1,3-dipolar cycloaddition/thermal rearrangement sequence, were converted by Wittig methylenation to the corresponding vinylcyclopropanes (VCPs), which underwent rearrang...

We have developed a general strategy for the synthesis of 2,5-syn disubstituted pyrrolidines that is based on the multi-faceted reactivity of the sulfone moiety and a 5-endo-trig cyclisation. This methodology was applied to the synthesis of indolizidine alkaloid monomorine I. Two factors were key to the success of this endeavour; the first was the choice of nitrogen protecting group whilst the ...

Indolizidine alkaloids constitute a very important class of natural products. These metabolites derived from lysine can be isolated from diverse sources, like fungi, bacteria, higher plants, invertebrates, and vertebrates. Their core structure is characterized by fused sixand five-membered rings, with a bridgehead nitrogen atom, and is found in 25–30% of all naturally occurring alkaloids. The m...

A concise enantioselective synthesis of the advanced intermediate 5 for the synthesis of pumiliotoxins (Gallagher's intermediate) is described. The synthesis started from the regio- and trans-diastereoselective (dr = 98:2) reductive 3-butenylation of (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14. After O-desilylation and Dess-Martin oxidation, the resulting keto-lactam 10 was subjected to a ...

found in amphibian skin, and the 5,8-disubstituted indolizidines, one of the largest subclass of these alkaloids, were detected from skin extracts of the poison-frog. Quite recently, we have found the synthetic 5,8-disubstituted indolizidine 235B (1), isolated from Dendrobates pumilio, acted as a potent noncompetitive and selective blocker of a4b2 nicotinic receptor (IC50 74 nM). The sensitivit...

X-ray crystallographic analysis of the title hydro-bromide salt, C(10)H(20)N(+)·Br(-), of (1R,2S,3R,5R,8aR)-3-hydroxy-meth-yl-5-methyl-octa-hydro-indolizine-1,2-diol defines the absolute and relative stereochemistry at the five chiral centres in steviamine, a new class of polyhydroxy-lated indolizidine alkaloid isolated from Stevia rebaudiana (Asteraceae) leaves. In the crystal structure, mol-e...