2.5- Dideoxy-2,5-imino-D-mannitol

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. 

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. ... 

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. ... 

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... 

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 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). ... 

Several imino-alditols have been prepared from non-carbohydrate sources. 2,S-Dideoxy-2,S-imino-D-mannitol has been synthesized from a pyroglutamic acid derivative (see Vol. 27, p. 209, ref. 59 for the use of pyroglutamic acid in the synthesis of other imino-alditols), and 1-deoxy-L-allonojirimycin has been made from a protected L-serine derivative. A protected D-serine aldehyde provided access to a l,2,4-trideoxy-l,4-imino-D-eryrAro-pentitol derivative for incorporation into DNA, and reduction of the minor natural amino acid, 4-L-hydroxyproline, gave l,3,4-trideoxy-l,4-imino-D-eryrAro-pentitol which, after Af-acylation with a fluorescent probe, was incorporated into oligonucleotides. ... 

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... 

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-... 

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. 

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. ... 

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