Reaction of 1‐α‐Cyano‐1‐deoxynojirimycin with Grignard Compounds—Complete Exchange of the CN— Group

Abstract

The direct biotransformation of (4a) into (Sa), however, proceeded in only low yields owing to the instability of the aminoketone (5a), the amino group being free. Protection of the amino function by a benzyloxycarbonyl group proved especially favorable, since both (46) as well as (5b) crystallize particularly well and deblocking of (5b) can be achieved in one step with ring-closure to give the l-deoxynojirimycin ( I ) .Reaction of (4a) with benzyloxycarbonyl chloride in water at pH=8-10 afforded (4b), which could be quantitatively oxidized with Gluconobacter oxydans to (Sb). The yield was more than 90%, for a conversion of 60-80 g per liter of culture medium. The hydrogenation of (Sb) in methanollwater led stereoselectively[61, with removal of the protecting group and ring-closure, to 1-deoxynojirimycin Using the same synthetic sequence, we were also able to prepare some N-alkyl-1 -deoxynojirimycin derivatives[31 and-starting from D-mannose-the manno-isomer of (I), 1,5-dideoxy-1,5-imino-~-mannitol~'~ (yield 14%). (1j. Procedure(56): 7 L of nutrient medium (H20, 5% sorbitol, 2% Ohly yeast extract, 0.4% K2HP04, pH=6.5 with KOH) is autoclaved in a 1OL fermenter for 45 min at 121"C, inocculated with Gluconobacter oxydans''] (250 mL pre-culture, same medium), and incubated for 24 h at 30°C, 10 L air/ min, 500 rpm. The culture is treated 5 times at intervals of 24 h with a hot (80-90°C) solution of 100 g (46) (m.p. 142-144 "C, from water) in 750 mL of water. After 2d (56) begins to crystallize out, after 6d the fermentation is finished. The precipitate is filtered off by suction, dissolved in 6 L of methanol and the cell residues separated; the solvent is removed in a rotary evaporator and the residue recrystallized from 2-propanol. Yield 455 g (92v0), m.p.

Glycomimetics: A Versatile de Novo Synthesis of β-1-C-Aryl-deoxymannojirimycin Analogues

“…To our knowledge only two such compounds have been reported. Junge reported the synthesis of α-1- C -phenyl-deoxynojirimycin ( 7a ), and Fleet reported the synthesis of β-1- C -phenyl-deoxymannojirimycin ( 8a ). ,9b Of the two reports, only Fleet presents biological studies. As is common with most C 1 -substituted deoxymannojirimycin derivatives, the β-phenyl derivative 8 shows no inhibition of mannosidases, but is a potent inhibitor of α- l -fucosidase.…”

Chemical Synthesis of β-Homonojirimycin, of Its N-Butyl Derivative, and of “Methyl Homoazacellobioside”

“…This proposition is supported by the potent activity of the 7- O -β- d -glucopyranosyl derivative of 1 7 toward intestinal sucrase and other disaccharidases of the digestive system. Few other types of aza- C -glycosyl compounds have been described so far: − therefore particularly noteworthy are the recent first examples of aza- C -disaccharides. ,

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Tactics and strategies for the synthesis of iminosugar C-glycosides: a review

“…By analogy with C-glycosides, 12,13 the replacement of the oxygen atom of the N,O-acetal function by a methylene group to form a stable C-C bond at C-1 has been a frequently used tactic to generate stable analogues of glycoconjugates. The first synthesis of iminosugar C-glycosides was performed by Bayer's chemists in the early 1980s, 14 almost 10 years before natural a-homonojirimycin 2, one of the simplest examples of this class of compounds, was isolated for the first time. 15 Since this pioneering work, which was triggered by the therapeutic interest of iminosugars, many synthetic efforts have been devoted to developing efficient and stereocontrolled routes to iminosugar C-glycosides.…”