SYNTHESIS OF A GLUCOSE-DERIVED TETRAZOLE AS A NEW BETA-GLUCOSIDASE INHIBITOR - A NEW SYNTHESIS OF 1-DEOXYNOJIRIMYCIN

The tetrazole 1 is a new beta-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 110-125-degrees. 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-idonontrile 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 18 and 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.