Of -indolizidine alkaloids

Another Rhn-catalyzed decomposition of a a-diazoester as described by Sabe and coworkers [198] was used for the synthesis of indolizidine alkaloids (Scheme 6/2.8). It can be assumed that, first, an ammonium ylide is formed which then undergoes a 1,2-shift with ring-expansion. Thus, reaction of 6/2-40 with Rh2(OAc)4 led to a 72 28 mixture of 6/2-41 and 6/2-42 in 85 % yield. Cu(acac)2 can also be used with even better yields, but lower selectivity (65 35). 

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

Dreyer, D. L., Jones, . C. and Molyneux, R. L. (1985). Feeding deterrency of some pyrrolizidine, indolizidine, and quinolizidine alkaloids towards pea aphid (Acryrthosiphon pisum) and evidence of phloem transport of indolizidine alkaloid swainsonine. Journal of Chemical Ecology 11 1045-1051. 

Daly, J. W., Tokuyama, T., Fujiwara, T., Highet, R. J., Karle, I. L. A new class of indolizidine alkaloids from the poison frog, Dendrobates tricolor. X-ray analysis of 8-hydroxy-8-methyl-6-(2 -methylhexylidene)-1-azabicyclo[4.3.0]nonane, J. Am. Chem. Soc. 1980, 102, 830-836. 

The perhydroindolizine, named indolizidine, is the alkaloid <5-coniceine. There is a great number of indolizidine alkaloids. Since the chemistry of these alkaloids is reviewed regularly (see Sections 3.08.4 and 3.08.6 for references), only selected topics from the natural products field will be treated here. 

Synthetic approaches to stereoisomers and analogs of indolizidine alkaloid castanospermine 92T4045. 

Interestingly, all other diols, tried as a protecting group on the acetal, led to lower diastereoselectivity of the addition. This synthetic strategy was used in the synthesis of indolizidine alkaloids,279 bis(l-arylethyl)amines,280 a protease inhibitor.281 The addition reaction of 1,2-bisimines, easily available from glyoxal and chiral cr-phenylethy-lamine, gives under optimized conditions a diastereomerically pure product, that was converted to a chiral 1,2-diamine. Interestingly, decrease of the temperature below the optimum (50 °C) leads to a sharp drop of the stereoselectivity (Scheme 96).282... 

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... 

Another fascinating intramolecular process involves the spirocyclic epoxide 103, which carries a pendant azide group. Under the influence of ethylaluminum chloride, this substrate undergoes Lewis acid assisted cyclization followed by an intramolecular Schmidt reaction and subsequent in situ reduction of the intermediate iminium species 105 upon addition of sodium borohydride. This protocol was used as a key step in a novel synthesis of indolizidine alkaloids of pharmaceutical interest <03OL583>. 

The asymmetric synthesis of indolizidine alkaloids is described utilizing a palladium-catalyzed amination process. Ionization of an allylic carbonate provides a symmetrical rr-allyl palladium complex, subsequent reaction with a protected homoallylamine gave the product in 93% yield and >99.5% ee (eq 5). ... 

The earlier literature pertaining to this small group of indolizidine alkaloids was described in Volume 28 of this treatise (/). More recent coverage may be found in a general survey of indolizidine alkaloids from plant and fungal sources 14), and in a review on the synthesis of indolizidine alkaloids (555). 

A new family of indolizidine alkaloids has been isolated from three species of the Elaeocarpus genus (fam. Elaeocarpaceae). E. polydactylus Schltr., a large, spreading tree, indigenous to New Guinea, contains three interrelated alkaloids of... 

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... 

The synthesis of indolizidine alkaloids, including tylophorine and 6-coniceine as well as Elaeocarpus alkaloids, by the intramolecular imino Diels-Alder method (cf. vol.12, p.71) has been pub-... 

Intramolecular tandem Michael addition-amide formation in the intermediate (291) afforded an epilupinine precursor (Scheme 60) <89H(29)1209>. Another quinolizidine synthesis forming two a bonds in its key step is the reductive double alkylation of azido epoxides with an (o leaving group (292). This strategy has been applied to the synthesis of ring-expanded analogues of indolizidine alkaloids (e.g. (293)) from D-arabinose (Scheme 61) <93TL822l>. 

B.I. The Claisen Condensation. A classical reaction is the condensation of an ester enolate with an ester, illustrated by the self-condensation of ethyl butanoate in the presence of sodium ethoxide to give 3-keto-ester 167. Initial reaction with the base, under thermodynamic control in this case, generates the enolate anion (165). This anion attacks the carbonyl of a second molecule of ethyl butanoate to give 166. Displacement of ethoxide generates ketone 167. As shown here, this reaction is known as the Claisen condensation. A synthetic example is taken from Lubell s synthesis of indolizidine alkaloids, in which diester 168 was treated with LiN(SiMe3)2 in THF at -78°C to give the self-condensation product 169, in 52% yield. 

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