Indolizidines structures

An intense NOESY cross peak between H-1 and H-5 is only compatible with a cw-fused indolizidine structure having an axial iV-lone pair on the piperidine ring. The GC-FTIR spectra showed weak Bohlmann bands,... 

No alkaloids had been obtained from the family Elaeocarpaceae until a CSIRO group began a study of certain Elaeocarpus spp. from New Guinea. Amongst a score or so of alkaloids they isolated was a new indole base, elaeocarpidine (7), but most of the others had novel indolizidine structures exemplified by elaeokanine C (8), elaeokanidine A (9) and elaeocarpine (10) [28]. 

The product of the reaction in Entry 8 was used in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxy group is determined by the structure of the oxazoline ring formed in the cycloaddition. Entry 9 portrays the early stages of synthesis of the biologically important molecule biotin. The reaction in Entry 10 was used to establish the carbocyclic skeleton and stereochemistry of a group of toxic indolizidine alkaloids found in dart poisons from frogs. Entry 11 involves generation of a nitrile oxide. Three other stereoisomers are possible. The observed isomer corresponds to approach from the less hindered convex face of the molecule. 

The X-ray analysis of compound 2 (Figure 2) was used to confirm its structure and revealed that only the carbomethoxy group at C-l lies on the plane of indolizine nucleus as already evidenced for other 1,2,3-trisubstituted indolizidines <2000CHE1192>. 

The NMR spectra of indolizidine derivatives have already been described accurately <1984CHEC(4)443 1996CHEC-II(8)237> more recently, the extensive use of mono- and bidimensional H and 13C NMR spectra allowed the structural assignment of natural compounds such as grandisine A possessing an indolizidine nucleus (Figure 3) <2005JOC1889>. 

Table 1 Structure of indolizidine alkaloids (bicyclic gephyrotoxins) synthesized since 1995...

Another class of these amphibian alkaloids, the pumiliotoxins, contain an alkylidene side chain on C-6 of the indolizidine ring (Table 2). Due to their myotonic and cardiotonic activity, and challenging structure, they also have been the object of synthetic interest. A review points out the state of the art at the beginning of the decade <1996CRV505>. 

The structural features of the solanum alkaloids are based on two primary skeletal configurations solanidane, with or without glycoside functionalities, as featured by the toxic and teratogenic steroidal alkaloids a-chaconine and a-solanine with the indolizidine type E-F ring (Figure 2.7a) and the spirosolane... 

Indolizidine alkaloids contain the indolizidine nucleus with two different cycles. The structural development of this kind of alkaloid is presented in Figure 53. 

The a is L-lysine, as in the case of piperidine, but the f3 is different. The /3 is a-aminoadipic acid 6-semialdehyde. The q> is L-pipecolic acid, which is synthesized in plants from piperideine-6-carboxylic acid. In the case of many other organisms, the obligatory intermedia (q>) is derived from the /3. The

ring structure. The indolizidine nucleus will be formed only in the synthesis of the x- The deep structmal change occms when

Claisen reaction with acetyl or malonyl CoA (Cra/mCoA) and the ring closme process (by amide or imine) to 1-indolizidinone, which is the x- The second obligatory intermedia ( k ) only has the indolizidine nucleus. 

Tables I through VIII summarize the occurrences of alkaloids from ants and other insects. Each table presents chemical structures as well as specific sources of particular types of alkaloids e.g.. Table I covers piperidines and pyridines. Table II, pyrrolidines, pyrroles, and indolizidines.

Methylation of indolizidine gave a mixture of trans and cis fused methiodides (19) and (20), the structures of which have been substantiated by a comparison of the NMR spectra with those of the corresponding quinolizidine methiodides. 

Indolizidine is the alkaloid S-coniceine and this nucleus has been observed in several groups of alkaloids. Since the chemistry of alkaloids deriving from indolizidines and partially unsaturated indolizidines is reported regularly (B-81MI30800, B-79MI30800), only selected examples will be taken from the natural products field. Structurally more complex alkaloids such as (217), (218) and indolizidine aza steroids (81H(16)1093,81H(16)1097), which may often be assigned to other groups of alkaoids as well, are not mentioned. 

The positions of the double bonds in such enamines appear to be controlled by the same factors that affect the stability of simple olefins and not by those which affect the enamines from many cyclic ketones.263 The products of mercuric acetate oxidation of some indolizidines, with yields, are shown in structures 213-217. The double bond positions were ascertained by comparing the IR and NMR spectra with 218 and 219. 

A detailed spectroscopic study has shown that swainsonine, from Swainsona canescens (Benth.) A. Lee, is 8a/3-indolizidine-la,2a,8 3-triol (1), and the structure and relative configuration have been confirmed by X-ray crystallography.1 Swainsonine is a potent inhibitor of a-mannosidase, and in animals it produces an accumulation of mannose-rich oligosaccharides in the lysosomal system of cells, leading to organ dysfunction and clinical disease.1... 

The alio series of the pumiliotoxin A class have an additional hydroxyl group that has been placed at C-7 on the indolizidine ring, without assignment of configuration. Three members of the alio series have been assigned the tentative structures (7), (8), and (9).3 Pumiliotoxins A and B are relatively toxic, and comparable in potency to strychnine. Pumiliotoxin B has a potent cardiotonic and myotonic activity.3 An enantioselective total synthesis of pumiliotoxin A alkaloids from L-proline has already been announced.4... 

Carbon-13 n.m.r. assignments have been reported for a number of isomeric 3-butyl-5-methyloctahydroindolizines that were synthesized in studies of the trial pheromone of the Pharaoh ant, and for some closely related indolizidines. This work includes a detailed discussion of the preferred conformations of these compounds.15 Securinegine, a minor alkaloid from Securinega suffruticosa Rehd., is isomeric with securinine, and the structure (22) has been proposed.16... 

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