Synthesis of a Glucose‐Derived Tetrazole as a New β‐Glucosidase Inhibitor. A New Synthesis of 1‐Deoxynojirimycin

The tetrazole 1 is a new β‐glucosidase inhibitor ( IC 50 =8·10 −5 M , Emulsin), obtained (92%) by deprotection of 22 , the product of an intramolecular cycloaddition of the azidonitrile 20 . This azidonitrile was formed as an intermediate by treating the L ‐ ido ‐bromide 14 or the L ‐ido‐tosylate 19 with NaN 3 at 110–120°. It was isolated in a separate experiment. The yield of 22 from 19 reached 70%; 21 was formed as by‐product (10%). The bromide 14 (42%) and the iodide 15 (30–35%) were obtained from the nitrile 13 , together with the 2,5‐anhydro‐ L ‐idononitrile 16, which was formed in ca. 35–45%. The tosylate 19 was obtained from 18 (97%). To obtain 18 , the nitrile 13 was oxidized according to Swern (→17, 92%) and then reduced (NaBH 4 , CeCl 3 ), leading to 18 and 13 (92%, 18/13 93:7). Reduction of the tetrahydropyridotetrazole 22 with LiAlH 4 afforded 83 % of the piperidine 23 , which was deprotected to (+)‐1‐deoxynojirimycin hydroacetate (2·AcOH, 86%) and further converted into the corresponding hydrochloride and into the free base 2 .