Deoxynojirimycin structure

A model for the structural relationship of /V-butyl-1 -deoxynojirimycin (131, Scheme 33) with ceramide, the substrate of ceramide glucosyltransferase, was suggested by Butters and coworkers. They conducted a comparative investigation on a range of 14 derivatives of 1-deoxynojirimycin substituted at the ring nitrogen and/or C-l, as well as 5 pyrrolidine-type inhibitors selected by superpositioning of the iminoalditol with a portion of the ceramide structure.364... 

E. M. S. Harris, A. E. Aleshin, L. M. Firsov, and R. B. Honzatko, Refined structure of the complex of 1-deoxynojirimycin with glucoamylase from Aspergillus awamori var. X100 to 2.4-A resolution, Biochemistry, 32 (1993) 1618—1626. 

R. Kanai, K. Haga, K. Yamane, and K. Harata, Crystal structure of cyclodextrin glucanotransferase from alkalophilic Bacillus sp. 1011 complexed with 1-deoxynojirimycin at 2.0 A resolution,. /. Biochem., 129 (2001) 593-598. 

B. Brumshtein, H. M. Greenblatt, T. D. Butters, Y. Shaaltiel, D. Aviezer, I. Sihnan, A. H. Futerman, and J. L. Sussman, Crystal structures of complexes of iV-butyl- and iV-nonyl-deoxynojirimycin bound to acid P-glucosidase. Insights into the mechanism of chemical chaperone action in Gaucher disease,... 

The simple piperidine pelletierine from Punica granatum (pomegranate) (Punicaceae) and Duboisia myoporoides (Solanaceae) is an anthelmintic. The simple piperidine derivatives deoxy-mannojirimycin (DMJ) and deoxynojirimycin (DNJ) from Lonchocarpus species (Fabaceae) are glycosidase inhibitors because they are structurally similar to the pyranose (six-membered ring) sugar moieties of the glycosidase disaccharide substrates. 

Following the discovery of l-deoxynojirimycin 2 as a fermentation product with pronounced inhibitory effects on mammalian a-glucosidases, a novel therapeutic principle for the treatment of certain types of diabetes was postulated. Because of adverse side effects of the parent compound, a wide range of structurally altered analogs (Figure 9.19) have been synthesized and screened. 

Fig. 5 Structures of the presumed oxocarbenium ion of glucose and the protonated forms of deoxynojirimycin and isofagomine, potent inhibitors of many jS-glycosidases.

---