Glycosidase inhibitors natural

Asano, N., Nash, R. J., Molyneux, R. J., Fleet, G. W. J. (2000). Sugar-mimic glycosidase inhibitors natural occurrence, biological activity and prospects for therapeutic application. Tetrahedron-Asymmetry, 11, 1645-1680. 

The total syntheses of the potent glycosidase inhibitors (+)-castanospermine, (+)-6-epicas-tanosperimine, (+)-australine, and (+)-3-epiaustraline have been reported. These four natural products are derived from a single common intermediate, the nitroso acetal (as shown in Scheme 8.43), which is created in the key step by the asymmetric tandem [4+2]/[3+2] cycloaddition between silaketal nitroolefin and chiral vinyl ether.182 The strategy of the synthesis is outlined in Scheme 8.43. Scheme 8.44 presents a total synthesis of (+)-castanosperimine and (+)-6-epi-castanosperimine from the common intermediate prepared by tandem [4+2]/[3+2] cycloaddition. 

The synthesis of a bridgehead sulfonium salt analogue 59, of the naturally occurring glycosidase inhibitor castanospermine, proceeded by a multistep procedure starting from 5-thio-d-glucopyranose pentaacetate <2000JA10769>. The desired bicyclic sulfonium salt 57 could not be obtained from the key bromide precursor... 

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

FIG. 2. Polyhydroxylated azepanes 9-13 that have been assayed as glycosidase inhibitors. These structures were inspired by the natural-product glycosidase inhibitors nojirimycin (14) and fagomine (15). 

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... 

Lillelund, V.H. et al. Recent Developments of Transition-State Analogue Glycosidase Inhibitors of Non-Natural Product Origin. 2002 [23]... 

Johnston, B D, Ghavami, A S, Jensen, M T, Svensson, B, Pinto, B M, Synthesis of selenium analogues of the naturally occurring glycosidase inhibitor salacinol and their evaluation as glycosidase inhibitors, J. Am. Chem. Soc., 124, 8245-8250, 2002. 

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