Conduritol epoxides

Conduritol Epoxides (1,2-Anhydroinositols) and Sugar-derived Epoxides. 364... 

The specific reaction of a conduritol epoxide requires, in addition to the acidic group for the protonation of the oxirane, a nucleophile for the formation of the covalent bond. In all cases studied so far, this is the carboxylate... 

The wide scope of the application of conduritol epoxides for the active-site-directed inhibition is seen from the data given in Table XI. Only a few... 

Kinetic Constants for the Inactivation of Glycosidases by Conduritol Epoxides Corresponding to their Respective Glycon Specificities (see Text)... 

Despite a higher intrinsic reactivity, epoxides of type 35 and 36 show a lower inactivation rate kj(max), as seen in Table XI, than the conduritol epoxides. This is probably caused by the greater flexibility of the epoxyalkyl chain in the active-site cleft, and by non-productive binding in positions where the oxirane is not within reach of the catalytic groups of the active site. For epoxypropyl oligosaccharides, this would hold even when the inhibitor occupies the correct subsites. 

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-... 

Labeling experiments with conduritol epoxides have permitted determination of the amino acid sequence around the essential aspartate (glutamate) with the following results. 

Unsurprisingly, the nitrogen analogue of conduritol epoxide inactivated GH 13 yeast ot-glucosidase and a GH 1 p-glucosidase from Agrobacterium faecalis the inactivation appeared faster than with conduritol B epoxide itself. 

It is convenient to divide the inhibitors into two categories. The first is represented by reagents that form highly reactive products after catalytic conversion. These inelude glycosylmethyl aryltriazenes (VIII) (235, 236), conduritol epoxides (IX) (46), 1M -difluoroalkylglyeosides (XII) (237), and two recently introduced aziridines derived from conduritol (X) (238) and deoxynojirimycin (XI) (239). 

The microbial oxidation of benzene and its derivatives using Pseudomonas putida have been used in several cyclitol syntheses. These include the preparation of conduritol D and the deuterated compound 99", D-cA/ro-inositol and D-cAiro-3-inosose for which the key step involves a one pot oxidation-protection to an epoxy-acetonide derivative," " and racemic quebrachitol." Also reported are the syntheses of (+)-D-chrro-inositol, a//o-inositol, muco-inositol and neo-inositol from a halogenated conduritol epoxide." ... 

---