DMDP

One last approach to thionocarbamates on carbohydrate scaffolds was developed in D-Fru series the intermediate imino sugar (2R,3R,4R,5R)-2,5-bis(hydroxymethyl)-3,4-dihydroxypyrrolidine (DMDP) obtained in... 

The condensation of DMDP with carbon disulfide/dicyclohexylcarbodiimide (DCC) afforded the indolizine derivative—potentially biological active thionocarbamate on carbohydrate scaffold, fused from the nitrogen side. 

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... 

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... 

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. 

C.-Y. Yu, N. Asano, K. Ikeda, M.-X. Wang, T. D. Butters, M. R. Wormald, R. A. Dwek, A. L. Winters, R. J. Nash, and G. W. J. Fleet, Looking glass inhibitors l-DMDP, a more potent and specific inhibitor of a-glucosidase than the enantiomeric natural product DMDP, Chem. Commun. (2004)1936-1937. 

The most significant indication that the biocatalytic properties also depend on the expression host comes from our studies on the fructose analogues DMDP 10 (2,5-dihydroxymethyl-(3S,4R)-dihydroxypyrrolidine) and 5-deoxy-D-fructose as inhibitors of SuSyl (Fig. 2.2.6.2). In contrast to SuSyl from yeast, the strongest inhibitor for recombinant SuSyl from E. coli is 10 (IC501.5 mM), suggesting that the enzyme prefers the D-fructofuranose conformation. 

Catalyst preformation in the presence of dienes is also favorable for the preparation of Nd-BR with a low solution viscosity and a low cold flow. These properties result from a high degree of branching and a low PDI. Nd-BR which meets these requirements is prepared with the catalyst system NdV/DIBAH/EASC. Catalyst preformation in the presence of IP and dimethyl-di-2,4-pentadienyl-(E,E)-silane (DMDPS, Scheme 11) are essential features. The optimized addition order for the catalyst components is DIBAH + IP + NdV. This catalyst mixture was aged at 50 °C for 90 min. Prior to the addition of the Cl-donor it is cooled to 5 °C. The catalyst was subse-... 

Table 15 Influence of catalyst preformation and DMDPS on Nd-BR properties [395,396]...

Adenophora triphylla war. japonica, whicii was grown at the medicinal plant garden in Japan, contains 6-C-butyl-DMDP (56) in addition to 1, 5, 24, 25, and 52 [45]. Interestingly, 6-C-butyl-DMDP and p-l-C-butyldeoxygalacTonojirimydn possess the same carbon backbone. Hence, both alkaloids could be biosynthesized by the five- or six-membered ring closure of a common precursor. 

While there may be phylogenetic reasons for particular distributions of the polyhydroxylated alkaloids in plants, caution should nevertheless be exercised in using the presence of these compounds as taxonomic markers. One reason is that these alkaloids can be released into the soil by producer plants and micro-organisms from where some, such as DMDP and castanospermine can be readily taken up and accumulated in plant tissues of completely unrelated neighbouring species. It may also be the case that micro-organisms (Rhizobium, other rhizosphere organisms, or endophytes) closely associated with specific plants may also produce polyhydroxylated alkaloids which could then be mistakenly considered of plant origin. 

C-butyl-DMDP Adenophora triphylla var. japonica (Campanulaceae) whole planP ... 

Deoxy-6-C-(2,5-dihydroxyhexyl)-DMDP Hyacinthoides non-scripta (Hyadnthaceae) fruits/stalks Scilla campanulata (Hyacinthaceae) bulb ... 

C-butyl-DMDP good P-glucosidase inhibitor and poor inhibitor of P-galactosidase ... 

Deoxy-6-C-(2,5- dihydroxyhexyD-DMDP moderate inhibitor of amyloglucosidase and weak inhibitor of a-fucosidase"... 

Nematicidal Properties. Crop damage by plant parasitic nematodes is estimated to amount to around 20% of the world s crop production causing serious economic damage. Experiments with 2,5-dideoxy-2,5-imino-D-mannitol (DMDP 3) have revealed that potato cyst nematodes were considerably damaged in the presence of this compound. Its potential as a foliar spray, soil drench and seed coating has been suggested. Not clear, as yet, is DMDP s mode of action in this context [222]. 

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