1.5- Imino-D-glucitol

Deoxynojirimycin (2) 1,5-Dideoxy-1,5-imino-D-glucitol Xylose isomerase (EC 5.3.1.5) 1DIE 245... 

The paradigmatic hexosaminidase inhibitor with basic nitrogen in the ring, 2-acetamido-1,2-dideoxynojirimycin (2-acetamido-l,2,5-trideoxy- 1,5-imino-D-glucitol, 33) has not been found naturally to date. This inhibitor was first prepared by Fleet and co-workers [76,77] in a 17-step synthesis from D-glucose via methyl 3-0-benzyl-2,6-dideoxy-2,6-imino-a-D-mannopyranoside together... 

Treatment of the D-arabino- and D-xylo-furanosides 1 and 2 with DAST afforded the deoxyfluoro derivatives 3 and 4 in the former case, whereas the latter gave the anhydro-sugar 5 and the deoxyfluoro compound 6 (Scheme 1). Osmium tetroxide-catalysed dihydroxylation of the chiral unsaturated derivative 7 led to the synthesis of 2-deoxy-2-fluoro-D-xylose and -L-lyxose." 1,2,5-Tri-deoxy-2-fluoro-1,5-imino-D-glucitol and 1,2,5-trideoxy-1 -fluoro-2,5-imino-D-... 

Dideoxy-1,5-imino-D-glucitol, 9CI. Moranoline. 1-Deoxynojirimycin. S-GI. Antibiotic S-GI [19130-96-2]... 

Examples of other fluorinated inhibitors, mainly of D-glucosidases, are the 2-deoxy-2-fluoro derivative 106 (Scheme 27) of miglitol (A-hydroxyethy I -1 -deoxynoj i i i my-cin, 107),229 4-deoxy-4,4-difluoroisofagomine (108),230 3-deoxy-3-fluoro-calystegin B2 (109),231 the 1-deoxyfluoro derivative (110) of 2,5-dideoxy-2,5-imino-D-mann-itol,232 as well as the 3-deoxyfluoro analogue (111) of nonnatural l-DMDP (2,5-dideoxy-2,5-imino-L-mannitol)233 and the 3-deoxy-3,3-difluoro derivative (112) of 2,5-dideoxy-2,5-imino-D-glucitol (113).234 All of these are weaker inhibitors than the parent compounds. l,4,6-Trideoxy-6-fluoro-l,4-imino-D-mannitol (114) was prepared by Winchester and coworkers.210... 

K. Dax, V. Grassberger, and A. E. Stiitz, Simple synthesis of l,5,6-trideoxy-l,5-imino-D-glucitol, the first fluorine-containing derivative of glucosidase inhibitor 1-deoxynojirimycin, J. Carbohydr. Chem., 9 (1990) 903-908. 

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. 

S. M. Andersen, M. Ebner, C. W. Ekhart, G. Gradnig, G. Legler, I. Lundt, A. E. Stiitz, S. G. Withers, and T. Wrodnigg, Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors, 1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol Syntheses and glycosidase inhibitory activities of l,2,5-trideoxy-2-fluoro-l,5-imino-D-glucitol and of l,2,5-trideoxy-l-fluoro-2,5-imino-D-mannitol, Carbohydr. Res., 301 (1997) 155-166. 

Figure 1. Diagram illustrating the common nomenclature for polyhydroxylated piperidine alkaloids, (a) 5-Amino-5-deoxy-D-glucopyranose has the trivial name nojirimycin, (b) 1-deoxynojirimycin (DNJ) is the trivial name for l,5-dideoxy-l,5-imino-D-glucitol and similarly (c) 1-deoxymannojirimycin (DMJ) is the common name for l,5-dideoxy-l,5-imino-D-mannitol.

A short synthesis of 3,4,6-tri-0-benzyl-l,5-dideoxy-l,5-imino-D-mannitol has been achieved by acid-catalysed hydrolysis, followed by controlled reductive amination of a per-benzylated l,6 -diazido-l,6 -dideoxy-sucrose derivative. Further transformation by way of an azide displacement of a 2-0-triflyl derivative afforded ultimately 2-acetamido-l,2,5-trideoxy-l,5-imino-D-glucitol (2-acet-amido-1,2-dideoxynojirimycin). ... 

Further examples have been reported of the addition of nucleophiles to the l,2 5,6-diimino-L-iditol derivative 48 resulting in 6-amino-2,5-imino-D-glucitol or 6-amino-1,5-imino-D-mannitol derivatives depending on whether the primary or secondary carbon of the 1,2- or 5,6-imino group in 48 was attacked. The same compound, 48, also served as starting material for 2,S-dideoxy-2,5-imino-D-glucitol. (See Vol. 23, p. 231, refs. 48 and 49). 

V,A -Diacetylchitobiose has been converted into the pseudo disaccharide, P-D-GlcNAcp-(l- 4)-2-acetamido-l,2,5-trideoxy-l,5-imino-D-glucitol by way of intermediate 62. This was oxidized and reduced to give the 5-OH epimer of 62, converted to a mesylate, reduced to the 1-amino compound (which effects cyclization) with displacement of mesic acid and finally de-benzyl-ated. ... 

The well known, D-mannitol-derived bis-aziridine 37 has been used to prepare 6-amino-6-deoxy-2,5-imino-D-glucitol and -1,5-imino-D-mannitol derivatives 38 and 39 as potential glycosidase inhibitors. Treatment of 37 with acetic add, or alternatively allyl alcohol in the presence of an ytterbium catalyst, afforded mono-O-acetylated or -allylated glucitol/mannitol mixtures in 2 1 and 1 2 ratios respectively. ... 

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