Novel Synthesis of the Glycosidase Inhibitor Deoxymannojirimycin and of a Synthetic Precursor d-lyxo-Hexos-5-ulose

Abstract

[reaction: see text]. The synthesis of D-lyxo-hexos-5-ulose (5-ketomannose, 1,5-dicarbonyl sugar), a synthetic precursor to the glycoprocessing inhibitor deoxymannojirimycin, was carried out by an in situ epoxidation and hydrolysis of a trimethylsilyl-protected 6-deoxyhex-5-enopyranoside followed by facile removal of the protecting groups. A novel nine-step synthesis of deoxymannojirimycin has also been achieved from methyl alpha-D-mannopyranoside; this involved methanolysis of epoxides derived from an acetylated 1-azido-6-deoxyhex-5-enopyranoside followed by deprotection and catalytic hydrogenation.

Synthesis of Somatostatin Mimetics Based on 1‐Deoxynojirimycin

“…The reaction was then stirred at room temperature under N 2 for 12 h. The solvent was removed under diminished pressure and chromatography (EtOAc) of the residue gave the tritylated intermediate. To this intermediate (450 mg, 0.523 mmol) in dry DMF (25 mL) at 0 8C, was added slowly NaH (190 mg of a 60 % disper- (9). The methoxytrityl derivative 8 (1.567 g, 1.87 mmol) was dissolved in MeOH/CH 2 Cl 2 (2:1, 65 mL) and concentrated H 2 SO 4 (30 mL, 0.4 mmol) was added slowly and the mixture was then stirred at room temperature for 12 h. Saturated NaHCO 3 was then added until the solution was neutral and the excess organic solvents were removed under vacuum.…”

“…This is presumably because they are not as readily available as pyranosides and their preparation is not trivial. [8,9] Potential advantages of investigating 1-deoxymannojirimycin (DMJ) [10] or 1-deoxynojirimycin (DNJ, 3, Figure 1) or other iminosugars compared with pyranosides as scaffolds include the possibility that the protonated ring nitrogen atom could contribute a charged hydrogen bonding group to enhance interactions of a particular ligand with a receptor. Also pharmacophoric groups can be grafted to the ring nitrogen.…”

Design, synthesis and biological evaluation of gentiopicroside derivatives as potential antiviral inhibitors

“…With the alcohol 4 in hands, some common atom or functional group in drug design, such as halogen [18], sulfur [19], and amino group [20] and so on, could be introduced at primary position. The alcohol 4 was smoothly converted to the corresponding iodide 5f and bromide 5e in good yield using Br 2 /Ph 3 P [21] and I 2 /Ph 3 P [22] system. Furthermore, the introduction of a triflate at C-6' in alcohol 4 afforded a unstable intermediate which was followed by displacement with thioacetate [ 23 ], thiomethoxide, azide [24], fluor [25] to yield the desired compounds 5a-5d in good yield at two steps.…”

Recent Advances in the Total Synthesis of Piperidine Azasugars

“…An elegant nine-step synthesis of DMJ (10) by the catalytic hydrogenation of an azidoacetal intermediate 105 has been published by Murphy et al, [55] as depicted in Scheme 11. The iodo derivative 100 was prepared from commercially available methyl α-d-mannopyranoside by exchange of iodine with the hydroxyl group at C-6 [56] followed by acetylation of the other hydroxyl groups.…”