Indolizidine alkaloids swainsonine from

Acylamino cyclization.l0 The indolizidine alkaloid (- )-swainsonine (3) has been synthesized by radical cyclization of the acylamine 1, derived from D-tartaric acid, to provide the indolizidinones 2 in 71% yield. Conversion to the alkaloid (3) included removal of the keto group by conversion to the thiolactam by Lawesson s reagent (97%) followed by desulfurization with Raney nickel (96% yield). 

Swainsonine is a trihydroxylated bicyclic indolizidine alkaloid with four chiral centres, whose relative stereochemistry was determined by X-ray crystallographic analysis and the absolute configuration was deduced on the basis of biosynthetic and asymmetric induction studies, and then confirmed by an enantiospecific synthesis from D-mannose [2a]. 

The following post-1986 reviews in this treatise provide the antecedents for several sections of this chapter. The important contribution of Takahata and Momose in Volume 44, entitled "Simple Indolizidine Alkaloids", covered the period 1986 to 1992, but dealt only with Elaeocarpus alkaloids, slaframine, polyhydroxylated indoUzidines such as swainsonine and castanospermine, and alkdoids fiiom ants and amphibians (2). This partial update is especially valuable as a guide to published totd syntheses of these alkaloids. Materi of relevance is also to be found in a number of reviews on more specialized topics. Numata and Ibuka reviewed the chemistry of alkaloids from ants and other insects in Volume 31... 

Polyhydroxylated indolizidine alkaloids, due to their biological activity, have attracted considerable synthetic interest. The total synthesis of ( —)-l-qp/-swainsonine (250) from the chiral imine 238 (Scheme 58) and the parallel synthesis of (+ )-2,8,8a-tri-qp/-swainsonine (252) from the enantiomeric threose A-benzylimine 251, prepared from natural L-tartaric acid, provide further examples of the utility of tartaric acid in meeting the challenge of complex syntheses. A stereospecific 4 + 4 homologation utilizing 2-(trimethylsiloxy)furan (178) pro-... 

Fig. 3.28 Indolizidine alkaloids from the Convolvulaceae (i) Hydrophilic polyhydroxy alkaloids (swainsonine, 2- p>i-lentiginosine see Sect. 3.5.3) and (ii) unique lipophilic indolizidine alkaloids occurring in Ipomoea alba, I. hardwickii, and I. turbinata (see Sect. 3.6)...

Indolizidine alkaloids [15] such as castanospermine and swainsonine are formed from pipecolic acid, an amino acid derived from lysine, which can be elongated by malonyl-CoA followed by ring closure. When protonated, these alkaloids are oxonium mimics strongly inhibiting glycosidases. 

Colegate, S. M., Dorling, P. R., and Huxtable, P. R. 1991. Swainsonine a Toxic Indolizidine Alkaloid from the Australian Swainsona species. In Toxicology of Plant and Fungal Compounds-Handbook of Natural Toxins, Vol.6, Keeler, R. R, and Tu, A. T, eds. New York, Marcel Dekker. pp. 159-189. 

It is well known that alkyl azides also behave as 1,3-dipoles in intramolecular thermal cycloaddition reactions. The formation of two carbon-nitrogen bonds leads to triazolines, which are usually not stable. They decompose after the loss of nitrogen to aziridines, diazo compounds, and heterocyclic imines. There are a limited number of examples reported in which the triazoline was isolated [15]. The dipolar cycloaddition methodology has been extremely useful for the synthesis of many natural products with interesting biological activities [16], In recent years, the cycloaddition approach has allowed many successful syntheses of complex molecules which would be difficult to obtain by different routes. For instance, Cha and co-workers developed a general approach to functionalized indolizidine and pyrrolizidine alkaloids such as (-i-)-crotanecine [17] and (-)-slaframine [18]. The key step of the enantioselective synthesis of (-)-swainsonine (41), starting from 36, involves the construction of the bicyclic imine 38 by an intramolecular 1,3-dipolar cycloaddition of an azide derived from tosylate 36, as shown in Scheme 6 [ 19). 

A number of alkaloids are derived from perhydroindolizine (indolizidine). Among them, swainsonine (40, (lS)-8afS-octahydro-la,2p,8P-indolizine triol) shows remarkable biological activity as an inhibitor of some types of cancer and a promoter of the organism-specific cancer defence. Several syntheses of swainsonine are reported [227]. 

---