1.4- dideoxy-l,4-imino-D-mannitol

D-Acosamine (2,3,6-dideoxy-3-amino-D-otraZ>mo-hexose) has been isolated from hydrolysis of the antibiotic sporoviridin/ which contains at least two acosamine moieties in addition to viosamine (4-amino-4,6-dideoxy-D-glucose). 2-Acet-amido-glucal has been isolated from the urine of patients with sialuria and 1,5-dideoxy-l,5-imino-D-mannitol is present in the legumes Lonchocarpus sericens. ... 

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... 

Chemical syntheses have allowed investigations of structure-activity relationships, e.g., for mannosidase inhibitors [129,130], Some potent new inhibitors have been produced such as l,4-dideoxy-l,4-imino-D-mannitol (DIM) (41), an azafuranose analogue of mannose [131] which is a good mannosidase inhibitor but unlike 1-deoxymannojirimycin it does not inhibit Golgi a-mannosidase I. 1-Deoxymannojirimycin is a more potent inhibitor of a-L-fiicosidase than of a-D-mannosidase [132], 1-Deoxyfuconojirimycin (l,5-dideoxy-l,5-imino-L-fucitol) (DFJ) (42) is a synthetic potent and specific inhibitor of human liver a-L fucosidase. 

AT-Methyl- and -butyl-derivatives of deoxynojirimycin, l,4-dideoxy-l,4-imino-D-arabinitol and 2,S-dideoxy-2,5-imino-D-mannitol have been studied by NMR spectroscopy to provide data for determining a conformational basis for the inhibition of glycosidase and HIV-1 replication activity by these types of compounds. ... 

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). 

Full details on the preparation of urethane derivatives of 3,4-di-O-benzyl-l,2,5,6-tetradeoxy-l,2 5,6-diimino-L-iditol from D-mannitol as well as the 3,4-dideoxy-L- Areo compounds 24 (R = C02 Bu or COiBn), from a hex-3-enitol, have been reported. (See Vol. 28, p. 230, ref. 66 for an earlier report). In both cases l,6-diamino-l,6-dideoxy-2,5-anhydroalditols were minor by-products. V-Boc-L-/V/o-l,2 5,6-bis-aziridino derivatives have proved to be versatile intermediates for the preparation of imino-alditols. For example, treatment of the 3,4-di-O-benzyl compound with diethylaluminium cyanide affords a 1 2 mixture of pyrrolidine 25 piperidine 26, and with dilithium tetrabromonickelate (Li2NiBr4) gives bromo-derivative 27 from which displacement of bromide allows further functionalization. ... 

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. 

Sulfonic esters of sugar alcohols often react similarly with ammonia thus, l,4 3,6-dianhydro-2,5-di-0-tosyl-D-mannitol and -sorbitol give326 the corresponding 2,5-diamino-2,5-dideoxy derivatives. However, 1,4 3,6-dianhydro-L-iditol affords326 a compound thought to be 1,4 3,6-dianhydro-2,5-dideoxy-2,5-imino-D-mannitol. 

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.

Fleet, G W J, Fellows, L E, Smith, P W, Synthesis of deoxymannojirimycin, fagomine, deoxynoj irimycin, 2-acetamido-1,5-imino-1,2,5-trideoxy-D-mannitol, 2-acetamido-1,5-imino-1,2, 5-trideoxy-D-glucitol, 25,3R,4R,5R-trihydroxypipecolic acid and 25,3R,4R,55-trihydrox3fpipecolic acid from methyl 3-0-benzyl-2,5-dideoxy-2,6-imino-a-D-mannofuranoside, Tetrahedron, 43, 979-990, 1987. 

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). ... 

The enzymatic conversion of 6-azido-6-deoxy-D-glucose into its D-fructose isomer was utilised as a key step in a five-step synthesis from sucrose [80] of the natural product and powerful D-mannosidase inhibitor 1-deoxymannojirimycin (l,5-dideoxy-l,5-imino-D-mannitol, 66) [81]. Subsequently, it was shown that the immobilised enzyme from Streptomyces murinus sp. (Sweetzyme T from Novo A/S) was able to isomerise D-glucose derivatives with modifications at C-3 and C-6 such as 6-azido-6-deoxy-3-0-methyl-D-glucose (67) as well as the corresponding 3-deoxy derivative 69 (Scheme 24) [64,82]. 

Instead to have the galacto-conflguratlon. A new acidic amino-sugar, 2,3-dia,cetamido-2,3-dideoxy-L-guluronlc acid, has been identified as a component of the 0-specific polysaccharide of a Pseudomonas aeruginosa strain this polysaccharide, on solvolysis with hydrogen fluoride, released the trlsaccharlde repeating unit (1) in almost quantitative yield. l,5-Dldeoxy-l,5-imino-D-mannitol, a recently Isolated plant natural product (Vol. 13, p.78),... 

Syntheses of 5-membered ring compounds have included an efficient four-step conversion of 1,3 4,6-di-O-benzylidene-D-mannitol to 2,5-dideoxy-2,5-L-iditol (38), the preparation of 1,4-dideoxy-l,4-imino-D-arabinitol and -D-lyxitol (39) from non-carbohydrate precur-sors (see also Chapter 24) and syntheses of 1,4-dideoxy-l,4-imino-... 

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