1- Deoxynojirimycin

Several possible models can be discussed for the molecular basis of slow inhibition, but experimental evidence in support of one or the other is still lacking for glycosidases. A reversible chemical reaction at the active site, for example, formation of the cyclic imine 3 or a diffusion-controlled association with a trace of 3 in equilibrium with the 5-araino-5-deoxypyranose 1 can be precluded, because slow inhibition is also observed with 1-deoxynojirimycin and its analogs and with acarbose (see Section II,2,d) and indoli-... 

A new type of mechanism-based enzyme-inactivators, which are related to conduritol epoxides with respect to activation at the active site, was introduced by Tong and Ganem, " who prepared the aziridine 37 from the o-galacto analog of 1-deoxynojirimycin. Compound 37 proved to be a pp-... 

Effects of Ionic Strength on the Inhibition of D-GIucosidases by 1-Deoxynojirimycin... 

Romaniouk, A.V., Silva, A., Feng, J., and Vijay, I.K. (2004) Synthesis of a novel photoaffinity derivative of 1-deoxynojirimycin for active site-directed labeling of I. Glycobiology 14, 301-310. 

CF3CN and CCI3CN leads to the corresponding substituted oxadiazolines (74, 829). Thus, reactions of (746) and (747), derived from 1-deoxynojirimycin with trichloroacetonitrile in toluene at room temperature leads to bicyclic compounds (748) and (749) (Scheme 2.308). 

Figure 3. Slow-onset of inhibition by 1 -deoxynojirimycin may be due to slow protonation of the inhibitor.

The group of Stiitz developed a convenient methodology of the transformation of maltose into 1-deoxynojirimycin derivative (Fig. 65).87... 

Von derOsten, C.H., Sinskey, A.J., Barbas El, C.F., Pederson, R.L., Wang, Y.F. and Wong, C.H., Use of a recombinant bacterial fructose-1,6-diphosphate aldolase in aldol reactions preparative syntheses of 1-deoxynojirimycin, 1-deoxymannojirimycin, l,4-dideoxy-l,4-imino-D-arahinitol, and fagomine. J. Am. Chem. Soc., 1989, 111, 3924. 

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... 

Family 10 xylanase Cex from Cellulomonas fimi and family 11 xylanase Bex from Bacillus circulans198,199 (the first being an anti-, the second a syn-protonator) were exposed to deoxynojirimycin-related (80, Scheme 22) and isofagomine analogous (81) xylosidase inhibitors, along with the anti-protonation-selective xylobiosyl... 

In the deoxynojirimycin series, the 6-deoxyfluoro derivative (91 p5.85) was the first published example of a deoxyfluoro analogue.218 This compound was also made available by Szarek and coworkers from L-sorbose.219 The 2-deoxyfluoro derivative (87),220 and subsequently l,4-dideoxy-4-fluoronojirimycm (96), was also reported.221... 

The 3-deoxyfluoro compound 97 (pZa 5.75) was published by Lee and coworkers222 who also synthesized the corresponding 3,6-difluoro derivative (98) of 1 -deoxynojirimycin.223,224... 

No direct comparison of the fluorinated castanospermine derivatives with the corresponding 1-deoxynojirimycin analogues has yet been conducted. In the castanospermine series, the fluorinated compounds exhibited low inhibitory activities. Only the 6-deoxyfluoro derivative 86 (corresponding to the 2-deoxyfluoro compound... 

In the 1-deoxynojirimycin series, the 2- (87), the 3- (97), and the 6-deoxyfluoro compound 91 (Scheme 24) were compared with the parent compound against a set of standard glucosidases.232 3-Deoxyfluoro (97, A) 0.35 pM) as well as 6-deoxyfluoro (91, 0.4 pM) derivatives exhibited a 40-fold decreased power with the a-glucosidase from rice (GH 31) as compared with the parent compound 2 (K, 0.01 pM at pH 6). Fagomine (1,2-dideoxynojirimycin, 3) was reported to have an IC50 of 320 pM with this enzyme.205... 

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