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

Publisher Website
Google Scholar
Abstract
The tetrazole 1 is a new β‐glucosidase inhibitor (IC50=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 NaN3 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 (NaBH4, CeCl3), leading to 18and 13 (92%, 18/13 93:7). Reduction of the tetrahydropyridotetrazole 22 with LiAlH4 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.