198691-31-5Relevant articles and documents
Chemoenzymatic preparation of novel cyclic imine sugars and rapid biological activity evaluation using electrospray mass spectrometry and kinetic analysis
Takayama, Shuichi,Martin, Richard,Wu, Jiangyue,Laslo, Karen,Siuzdak, Gary,Wong, Chi-Huey
, p. 8146 - 8151 (2007/10/03)
Cyclic imine sugars were prepared by a novel chemoenzymatic strategy in which azido-sugars, constructed by enzymatic aldol reactions, were hydrogenated under acidic conditions. These cyclic imine sugars were found to be potent inhibitors of glycoprocessing enzymes having K(i)'s in the nanomolar and micromolar range for a variety of glycosidases. In comparison with their fully hydrogenated counterparts the cyclic imine sugars generally showed comparable or better inhibition against the glycosidases tested. Because these cyclic imines are so readily available and since imines are key intermediates in a variety of cycloadditions, condensations, and nucleophilic additions, they are valuable as versatile synthetic intermediates for the preparation of navel iminocyclitols and derivatives. An example of such synthetic utility is demonstrated by the synthesis of amino-iminocyclitol 24 via a three-center, two-component Strecker reaction. A novel method for rapidly screening glycosidase inhibitors using electrospray mass spectrometry is also described and shown to be capable of identifying potent fucosidase inhibitors for detailed kinetic analysis. Also, in the reductive amination of azido-sugars for the preparation of the five-membered ring iminocyclitol 8, rhodium was found to exhibit superior face selectivity when compared to palladium or platinum catalysts.
