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

Abstract

The tetrazole 1 is a new 8-glucosidase inhibitor (IC50 = 8 . lo-' 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-idu-bromide 14 or the L-idu-tosylate 19 with NaN, at 1 1 0 -1 2 5 O . 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-~-idononitrile 16, which was formed in cu. 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, CeCI,), leading to 18 and 13 (92%, 18/13 93 :7). Reduction of the tetrahydropyridotetrazole 22 with LiAIH, 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.Introduction. -A number of glycosidase inhibitors, some of them with promising biological properties, have been isolated or designed. Among them are not only polyhydroxylated piperidines (e.g. 1-deoxynojirimycin (2) [I], nojirimycin (3) [2], and related compounds), polyhydroxylated pyrrolidines (e.g. DAB 1 [3]) and indolizidines (e.g. castanospermine (4) [4] and swainsonine [5]), but also analogues of glyconolactones (glucono-1,5-lactone [6], nojirilactame 5 [7], the amidine 6 [8], acylated hydroximolactones 7 [9], and lactone hydrazones 8 [lo]). 2 R = H 3 R = O H HO OH 7 R=OCONHPh

High Resolution X-ray Crystallography Shows That Ascorbate Is a Cofactor for Myrosinase and Substitutes for the Function of the Catalytic Base

“…1d) and gluco-hydroximolactam (Fig. 1e) were synthesized as described (9,11). C-GTL, the C-glycosidic analogue of glucotropaeolin (Fig.…”

Neighboring‐Group Participation in Nitrile‐Forming Beckmann Fragmentation Reactions: Synthesis of Enantiopure (E)‐2,3‐Di‐O‐substituted‐5‐methoxy‐ pent‐4‐enenitriles and Their Conversion into Pyranosylamines

“…Neither compound showed a CN absorption in their IR spectra, like other nitriles described in this work, and similarly to what has been previously observed for α-alkoxynitriles. [25,26] The structures of compounds 4a,b were confirmed by correlation with products obtained by known methods (Scheme 2). Starting from 5a, available from the O-benzyl derivative of -xylal [15,16] and in accordance with the reaction sequence depicted in Scheme 2, a compound identical to 4a, already prepared from 1a (see Scheme 1), was obtained.…”

Ti‐Mediated Synthesis of Aminocyclopropyl‐Substituted Carbohydrates

“…[14] Initial attempts to convert the oxime 5 into the nitrile 1 under the conditions described by Vasella et al (PPh 3 , CBr 4 ) [15] failed. Under these conditions, the removal of the labile 4,5-O-isopropylidene protecting group occurred, due to the effect of HBr formed in situ.…”