Indolizidine alkaloids structure

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. 

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

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

Juliprosopine from Prosopis juliflora A. DC. is a new type of indolizidine alkaloid, and on the basis of an extensive spectroscopic and chemical study it has been assigned the structure (2), in which relative configurations are shown for the substituents on the piperidine ring. Juliprosopine may be derived biosynthetically from combination of a dihydropyrrole unit with two Prosopis piperidine alkaloids that have C12 side-chains.2... 

Alder reaction [524, 525]. Danishefsky et al. have used nitroso dienophiles for the synthesis of mitomycin K and antibiotics of the FR 900482 family, the latter ones are structurally unique aziridino-l,2-oxazine derivatives [526-529]. An approach directed to the cephalotaxus alkaloids has been worked out by Fuchs et al. [530], and several indolizidine alkaloids have been prepared by Keck s [531] and Kibayashi s groups [532,533]. Kibayashi et al. also synthesised Nuphar piperidine alkaloids in enantiomerically pure form by means of an asymmetric nitroso Diels-Alder reaction [534]. 

Reports on new structures include the new alkaloid polycanthisine, isolated from the genus Astragalus [37], and a marine indolizidine alkaloid, stellattamide B, isolated from a Korean sponge. Fig. (20) [38]. 

Two further indolizidine alkaloids, juliprosinene ([a]o +9.5° for the chloride salt, c 0.04, CHCI3) and juliflorinine ([a]o +3.9°, c 0.03, CHCI3), were isolated from the leaves of Prosopis juUflora some years after the above work had been reported (299). Partial structures were once again deduced on the basis of extensive spectro-scopic comparisons with known alkaloids. Juliprosinene chloride, for instance, gave very similar spectra to juliprosine (319) and spectaline (320), and showed no doubling up... 

An indolizidine alkaloid isolated from the rhizomes of Polygonatum sibiricum (Liliaceae) also has some unusual features 311). The unnamed alkaloid, for which the structure 326 has been proposed on the basis of good spectroscopic data (IR, UV, MS H, C and HETCOR NMR), is the first 5,6,7,8-tetrahydroindolizine (cyclohexa[a]pyrrole) to have been found as a natural product. In addition, the ethoxymethyl substituent is unique, at least among the natural indolizidines. It should also be pointed out that simple indolizidine alkaloids have never before been isolated from liliaceous species. Although the structure 326 appears to be reasonable in the light of the spectroscopic evidence, judgement should perhaps be reserved until it can be confirmed independently. 

Secophenanthroindolizidine alkaloids and their secophenanthroquinolizidine analogs were last surveyed in Volume 28 of this series (i). A comprehensive review on the occurrence, structural elucidation, biosynthesis, synthesis, and biological activity of the phenanthroindolizidine alkaloids, including their seco variants, was published in 1987 (57P). The topic was also included in several more general reviews on indolizidine alkaloid chemistry 14,19,563). 

Removing the Me3Si and Boc groups and redrawing the structure reveals the amino acid 96 that cyclises in acid solution to bicyclic 97 having the skeleton of the indolizidine alkaloids. Further steps lead to (-)-petasinecine 98. This sequence looks involved but in fact only three intermediates are isolated 92, 96, and one between 97 and 98. 

Two pentacyclic bases containing tryptamine units and a second nitrogen have been reported. The structure (18) for nitrarine, an optically inactive base from Nitraria schoberi, relies at the moment on spectral measurements. Elaeocarpidine, an optically inactive alkaloid which co-occurs with indolizidine alkaloids in Elaeocarpus densijiorus, has been examined fully and proved to have the structure (19). Central to the structure determination was a hydro-genolysis, in acid solution, of the N-C-N system to give dihydroelaeocarpidine... 

A new series of indolizidine alkaloids has been isolated from the leaves of Elaeocarpus kaniensis Schltr., a rain-forest tree which flourishes in New Guinea.8 The structures of six of these alkaloids have been assigned on the basis of detailed spectroscopic studies, consideration of their biosynthesis and their presumed structural relationships with other alkaloids of the Elaeocarpus genus.9... 

Elaeocarpine, CieHigOaN (mp 81° [ajj, +0.1°) and isoelaeocarpine (mp 51° [a]u +0.4°) are two new indolizidine alkaloids of a new structural type. The complete structure and stereochemistry of elaeocarpine were determined by X-ray crystal structure analysis of its hydrobromide as LX. Its isomer, LXI, is obtained from LX by treatment with metha-nolic potassium hydroxide at room temperature. Spectral data are in accord with these structures (86). 

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