Alkaloid glycosidase inhibitors

Sinnlarly, f-i- -casuralme, a pentahydroxy pyrrolizidine alkaloid, is prepared by a tandem [4-i-3 /[3-i-3 cycloadchdon involving nitroalkene, chiral vinyl ether, and vinyl silane This process creates five of the six stereocenters present in this potent glycosidase inhibitor fScheme 8 35 ... 

Figure 10.31 Synthetic route to oxygenated pyrrolizidine alkaloids, and an aza-C-disaccharide as glycosidase inhibitors.

Recent research deals with stereoselective 1,3-dipolar cycloadditions of nitrones for the syntheses of alkaloids and aza heterocycles asymmetric synthesis of biologically active compounds such as glycosidase inhibitors, sugar mimetics, /3-lactams, and amino acids synthesis of peptido-mimetics and peptides chemistry of spirocyclopropane heterocycles synthesis of organic materials for molecular recognition and photochemical applications. 

Elbein AD, Molyneux RJ (1999) Alkaloid glycosidase inhibitors. In Pinto BM (ed) Comprehensive natural products chemistry, vol 3, chap 7. Elsevier, London... 

Molyneux, R.J., James, L.F., Ralphs, M.H., Pfister, J.A., Panter, K.E. and Nash, R.J. (1994). Polyhydroxy alkaloid glycosidase inhibitors from poisonous plants of global distibution Analysis and identification, in Colegate, S.M. and Dorling, P.R., Eds., Plant-associated toxins agricultural, phytochemical and ecological aspects, CAB International, Wallingford, pp. 107-112. 

Many glycosidase inhibitors are structurally related to natural substrates, closely resembling carbohydrates. However, several exceptions to this generalization are known. These include such diverse structures as the diterpene andrographolide and its analogues (38, Scheme 12),134 3,21-di-O-acetylcichoridiol (39, a triterpenoid),135 acridone alkaloids, and oriciacridone (40).136... 

Very few polyhydroxylated alkaloids are available commercially. Those which are available (principally DNJ, DMJ, castanospermine and swainsonine) have become standard reagents used to investigate the potential therapeutic and biochemical applications of this class of glycosidase inhibitor. So most of the following consideration of the therapeutic applications of polyhydroxylated alkaloids is based on a limited number of compounds that have been tested thoroughly, simply because these are the only ones which are readily available. It should also be noted that the doses required for beneficial effects in human disease states are generally below those causing the toxicides described in Section 1.4. 

For the most recent reviews see (a) Asano, N, Nash, R J, Mol3meux, R J, Fleet, G W J, Sugar-mimic glycosidase inhibitors natural occurrence, biological activity and prospects for therapeutic application. Tetrahedron Asymmetry, 11, 1645-1680, 2000 (b) Asano, N, Alkaloidal... 

Two new types of polyhydroxylated alkaloids containing dihydroxypyrrolidine moieties as glycosidase inhibitors from higher plants 02H(57)1539. 

Polyhydroxy Plant Alkaloids as Glycosidase Inhibitors and Their Possible Ecological Role... 

Polyhydroxylated alkaloids have been of great interest due to their activity as glycosidase inhibitors. These alkaloids, including 247, 250, and 251, were described in Volume five of this series [542]. A molecular modeling study has attempted to explain the inhibitory properties of these compounds [543]. Several reviews of these alkaloids are available [544-546]. 

The plant alkaloid castanospermine 155 and the related piperidine alkaloid 1-deox-ynojirimicin 160, like several other polyhydroxylated octahydroindolizidines, piperidines and pyrrolidines, are potent glycosidase inhibitors. These nitrogen bases are of considerable interest for the study of biosynthetic processes and, in addition, castanospermine and some of its derivatives may be of clinical value as antineo-plastic agents and as drugs in the treatment of AIDS. 

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