Iminosugars

FIGURE 9.17 Early examples of synthetic iminosugars and iminoalditols. 

FIGURE 9.18 Examples of biologically active sugar-related natural products with nitrogen in the ring. 

The large variety of biological activities found in these compounds and many of their derivatives was discovered to be based on their potent glycosidase [58,157], glycosyl transferase [158] and phosphorylase [159] inhibitory activities. 

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Three ring fused (5 5 5) heterocycle 60 on reduction with LiAlH4 gave triol 244 which was successfully converted in several steps to the iminosugar, 5-hydroxypiperidine-2,3-4,6-tetramethanol 245 (Scheme 42) <1999JOC8973>. 

The synthesis of enantiomerically pure D-manno and L-gluco iminosugars 183 and 184, respectively, was achieved via reduction of an isoxazoline to an amine, which subsequently acts as a nucleophile in a spontaneous opening of the cyclic sulfate moiety <06JOC894>. 

Iminosugars From Synthesis to Therapeutic Applications, ed. Ph. Compain and O. L. Martin, Wiley, 2007. 

Stiitz AE (ed) (1999) Iminosugars as glycosidase inhibitors nojirimycin and beyond. Wiley-VCH, New York... 

Miglustat (60 Zavesca ) 1 -Deoxynoj irimycin (DNJ) Iminosugar Semi-synthetic NP Microbial Type 1 Gaucher disease (GDI) Inhibits glucosylceramide synthase activity 215-217, 525-531... 

Steet R, Chung S, Lee WS, Pine CW, Do H, Komfeld S. (2007) Selective action of the iminosugar isofagomine, a pharmacological chaperone for mutant forms of acid-beta-glucosidase. Biochem Pharmacol 73 1376-1383. 

Steel R, Chung S, Wustman B, Powe A, Do H, Komfeld SA. (2006) The iminosugar isofagomine increases the activity of N370S mutant acid beta-glucosidase in gaucher fibroblasts by several mechanisms. Proc Natl Acad Sci USA 103 13813-13818. 

B. G. Davis, A silver-lined anniversary of Fleet iminosugars 1984-2009, from DIM to DRAM to... 

B. G. Winchester, Iminosugars From botanical curiosities to licensed drugs, Tetrahedron ... 

N. Asano, Naturally occurring iminosugars and related alkaloids Structure, activity and applications, in P. Compain and O. R. Martin, (Eds.), Iminosugars From Synthesis to Therapeutic Applications, Wiley, Chichester, 2007, pp. 7-24. 

M. S. J. Simmonds, G. C. Kite, and E. A. Porter, Taxonomic distribution of iminosugars in plants and their biological activities, in A. E. Stiitz, (Ed.), Iminosugars as Glycosidase Inhibitors, Wiley-VCH, Weinheim, New York, 1999, pp. 8-30. 

L. Nprskov-Lauritsen, and L. Agius, Iminosugars as potential inhibitors of glycogenolysis Structural insights into the molecular basis of glycogen phosphorylase inhibition,./. Med. Chem., 49 (2006) 5687-5701. 

B. La Ferla, P. Bugada, and F. Nicotra, Synthesis of the dimethyl ester of l-deoxy-i.-idonojirimycm-l-methylenephosphonate A new approach to iminosugar phosphorates,/. Carbohydr. Chem., 25 (2006) 151-162. 

O. Martin, Iminosugars Current and future therapeutic applications, Ann. Pharm. Fr., 65 (2007) 5-13. 

T. M. Wrodnigg, A. J. Steiner, and B. J. Uberbacher, Natural and synthetic iminosugars as carbohydrate processing enzyme inhibitors for cancer therapy, Anticancer Agents Med. Chem., 8 (2008) 77-85. 

G. Home, F. X. Wilson, J. Tinsley, D. H. Williams, and R. Storer, Iminosugars past, present and future Medicines for tomorrow, Drug Discov. Today, 16 (2011) 107-118. 

R. Zhang, W. Zhang, and T. Hu, Dextran glucosidase A potential target of iminosugars in caries prevention, Med. Hypotheses, 76 (2011) 574-575. 

Lundt I (2003) Iminosugars, isoiminosugars, and carbasugars from activated carbohydrate lactones efficient synthesis of biologically important compounds. In Witzak ZJ, Tatsuta K (eds) Carbohydrate synthons in natural products chemistry synthesis, functionalization and applications. ACS Symposium Series, vol 841. American Chemical Society, Washington, DC,pp 117-140... 

The second asymmetric synthesis deals with the preparation of a C-difluoromethyl iminosugar. The key step of this synthesis is a hetero-Diels-Alder reaction with a chiral imine of difluoroacetaldehyde (Figure 6.32). ... 

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