Imino-D-mannitol

Amino-1,5-anhydro-1 -deoxy-D-mannitol or 1,5-dideoxy-1,5-imino-D-mannitol trivial name deoxymannojirimycin... 

Another application of diastereoselective nitro-aldol reactions catalyzed by Bu4NF-3H20 is demonstrated in a simple synthesis of l,4-dideoxy-l,4-imino-D-mannitol (DIM) and amino analogues (Eq. 3.85).134 The nitro-aldol reaction of nitro compounds bearing a-oxy or a-amino function with glyceraldehyde leads to nitrohexitols, which can be reduced to the corresponding amino compounds. Cyclization gives iminopolyols, as shown in Eq. 3.85. 

In 1976, 1-deoxynojirimycin (2) was discovered as a natural product in a Moms species and coined moranoline.26 Incidentally, in the same year, a novel type of alkaloid was found in the liana plant, Derris elliptica, a native of Borneo but widespread in the tropics, and it was identified as 2,5-dideoxy-2,5-imino-D-mannitol (7, Scheme 3), also known as DMDP (2,5-dihydroxymethyl-3,4-dihy droxypyrrolidine).27... 

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... 

Interestingly, the furanoid derivative l,4,6-trideoxy-l,4-imino-D-mannitol (76, Scheme 20) was found a potent inhibitor of human oc-mannosidases and was comparable to the parent compound 19 (Scheme 7).210... 

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... 

Dideoxy-2,5-imino-D-mannitol 7 (Scheme 3) in complex (PDB 2AEY) with chicory fructan 1-exohydrolase (EC 3.2.1.153 GH 32) was found to bind in a similar way as does fructose, as well as the fructofuranosyl subunit of sucrose and... 

Somewhat unexpectedly, the 1-dansylamino derivative 193 (Scheme 58) of the 3-glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol turned out a nanomolar inhibitor (K 2.4 nM) of Agrobacterium sp. (3-glucosidase.382 The same was true when the fluorophor and the inhibitor were separated by a C6 spacer arm. Equally active were the corresponding coumarin-3-carboxylic acid derivative 66 (Scheme 18 ... 

A-(4-Dimethylamino)benzoyl-1 -amino-1,2,5-trideoxy-2,5-imino-D-mannitol (156)... 

G. W. J. Fleet, P. W. Smith, S. V. Evans, and L. E. Fellows, Design synthesis and preliminary evaluation of a potent a-mannosidase inhibitor l,4-Dideoxy-l,4-imino-D-mannitol, J. Chem. Soc., Chem. Commun. (1984) 1240-1241. 

G. Legler and E. Jiilich, Synthesis of 5-amino-5-deoxy-D-mannopyranose and l,5-dideoxy-l,5-imino-D-mannitol, and inhibition of a- and P-D-mannosidases, Carbohydr. Res., 128 (1984) 61-72. 

T. M. Wrodnigg, S. G. Withers, and A. E. Stiitz, Novel, lipophilic derivatives of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP) are powerful p-glucosidase inhibitors, Bioorg. Med. Chem. Lett., 11 (2001) 1063-1064. 

A. E. Hakansson, J. van Ameijde, L. Guglielmini, G. Home, R. J. Nash, E. L. Evinson, A. Kato, and G. W. J. Fleet, Looking glass inhibitors Synthesis of a potent naringinase inhibitor l-DIM (l,4-dideoxy-l,4-imino-L-mannitol), the enantiomer of DIM (l,4-dideoxy-l,4-imino-D-mannitol) a potent a-D-mannosidase inhibitor, Tetrahedron Asymmetry, 18 (2007) 282-289. 

A very powerful inhibitor, which is a bicyclic analogue of (33), is 6-acetamido-6-deoxycastanospermine (49), a compound synthesized from castanospermine and tested by Liu and co-workers [99]. This compound, amongst many other 6-modified castanospermine derivatives, was also prepared by the Furneaux team [100]. Furthermore, by controlled ring-contraction of suitably substituted castanospermine derivatives, these workers gained access to 8-acetamido-8-deoxyaustraline (50), a byciclic analogue of l-acetamido-l,2,5-trideoxy-2,5-imino-D-mannitol (44). This ring contraction reaction, which proceeds via a tricyclic aziridinium intermediate, is based on the same principle as the approach by Peter et al. to compound (45) [95]. 

Dideoxy-2,5-imino-D-mannitol (26), a nattural product found in Derris elip-tica as well as Lonchocarpus sp. [126], was obtained from L-sorbose via 5-azido-5-deoxy-D-ffuctopyranose (82) by Card and Hitz [127] and characterized as a very potent inhibitor of /3-D-fructofuranosidase (invertase). 

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