Iminoalditols

Fig. 13 Example of eight-membered ring iminoalditol obtained via RCM.

Selected from among their contributions were the first example of a synthetic furanoid iminoalditol, l,4-dideoxy-l,4-imino-D-mannitol (19, Scheme 7) 49 the first synthesis of the powerful L-fucosidase inhibitor l,5-dideoxy-l,5-imino-L-fucitol (20),50 the synthesis and structure confirmation of l,4-dideoxy-l,4-imino-D-arabinitol... 

Among furanoid iminoalditols, the 1-deoxyfluoro derivative 110 (Scheme 27) of... 

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... 

A. de Raadt, C. Ekhart, G. Legler, and A. E. Stiitz, Iminoalditols as affinity ligands for the purification of glycosidases, in A. E. Stiitz, (EdIminosugars as Glycosidase Inhibitors, Wiley-VCH, Weinheim, New York, 1999, pp. 207-215. 

J. Di, B. Rajanikanth, and W. A. Szarek, Fluorinated l,5-dideoxy-l,5-iminoalditols Synthesis of l,5,6-trideoxy-6-fluoro-l,5-imino-D-glucitol (l,6-dideoxy-6-fluoronojirimycin) and 1,4,5-trideoxy-4-fluoro-l,5-imino-D-ribitol (l,2,5-trideoxy-2-fluoro-l,5-imino-L-ribitol), J. Chem. Soc., Perkin Trans. 1 (1992)2151-2152. 

Using this type of chemistry, more than 30 different iminoalditols have been synthesised without using any protecting group strategy, and a number of new glycosidase inhibitors have been identified (2,12,13,14). Some selected interesting features will be discussed below. 

Eight-membered iminoalditols have been evaluated as inhibitors of glucuronidases <2004TL579>. 

FIGURE 9.17 Early examples of synthetic iminosugars and iminoalditols. 

Excellent examples for chiral pool access to various iminoalditols via Approach C were provided, for example, by Lundt and coworkers (Scheme 9.12) [170]. Additionally, an interesting chlorobenzene-based de novo access to mannojirimycin was reported by Hudlicky and his group (Scheme 9.13) [171]. 

Routes D and E have been frequently employed by Fleet and coworkers (Scheme 9.14) [172]. Symmetrical iminoalditols were made in a similar fashion by Dureault (Scheme 9.15) [173]. 

FIGURE 9.25 UDP-galactose mutase inhibiting iminoalditols with antibacterial properties. 

Inhibitors of Bacterial Cell Wall Biosynthesis. Interestingly, iminoalditol 81 (Figure 9.26) was found active against the Mycobacterium avium complex in an infected macrophage model at 4 p.g/ml [212]. Furthermore, this compound increased tumor necrosis factor a (TNFa) production in the infected cells. 

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