sp2-Iminosugars as chemical mimics for glycodrug design

Harnessing Multistep Chalcogen Bonding Activation in the α-Stereoselective Synthesis of Iminoglycosides

“…Particularly, iminosugar frameworks based on the glucose mimics such as Miglitol (Glyset) and Miglustat (Zavesca) had been approved for diabetic treatment and therapy in Gaucher and Niemann-Pick C diseases; 23 the galactose mimics such as Lucerastat and Migalastat (Galafold) had also found useful in chaperone-based therapy against Fabry disease. 23 Of particular recent interest is the emergence of α-sp 2 -iminosugars developed by Ortiz Mellet and co-workers as a useful glycomimetic, which possesses a broad biological activity profile. This includes potential anticancer and anti-inflammatory activities, toll-like receptor agonist activity, and use as a pharmacological chaperone for late-onset Tay-Sachs disease.…”

“…This includes potential anticancer and anti-inflammatory activities, toll-like receptor agonist activity, and use as a pharmacological chaperone for late-onset Tay-Sachs disease. 23,25 Prior studies demonstrated that the sp 2 -iminoglycosyl donors are also chemical mimics that imitate the glycosyl profile of normal monosaccharide donors. 26 Despite the wide-ranging uses of iminosugars, the synthetic development of stereoselective iminoglycosylations is very limited.…”

“…Of particular recent interest is the emergence of α-sp 2 -iminosugars developed by Ortiz Mellet and co-workers as a useful glycomimetic, which possesses a broad biological activity profile. This includes potential anticancer and anti-inflammatory activities, toll-like receptor agonist activity, and use as a pharmacological chaperone for late-onset Tay-Sachs disease. , Prior studies demonstrated that the sp 2 -iminoglycosyl donors are also chemical mimics that imitate the glycosyl profile of normal monosaccharide donors …”

A selenoureido-iminoglycolipid transported by zeolitic-imidazolate framework nanoparticles: a novel antioxidant therapeutic approach

“…, parasitic infections, a variety of cancers, and inflammatory diseases such as diabetic retinopathy and nephropathy). 16 Focused on this scenario, further advances have been achieved with the α-dodecylselenoureido-glycoside (referred to as DSeU, Fig. 1(A)) bearing a selenourea-type linkage at the pseudoanomeric position of the nojirimycin derivative.…”

Stereoselective Synthesis of Nojirimycin α-C-Glycosides from a Bicyclic Acyliminium Intermediate: A Convenient Entry to N,C-Biantennary Glycomimetics

“…Surprisingly, the reported examples of biantennary N -substituted iminosugar C -glycosides are rather limited. − An apparent reason is the complexity in accessing the C -glycoside precursors in pure diastereoisomeric form. Most of the current protocols involve intramolecular reductive amination , or aza-Wittig cyclization reactions, ,, with variable diastereoselectivity outcomes, or the use of 1- C -activated precursors that are themselves obtained as mixtures of diastereomers (Figure , left panel). , Sharply different, the 5 N ,6 O -oxomethylidenenojirimycin derivative 3 , (ONJ), a member of the sp 2 -iminosugar subgroup, is a chemically stable and configurationally defined compound that can be functionalized at the pseudoanomeric position via the corresponding acyliminium cation with total α-stereoselectivity (Figure , right panel). − Since the cyclic carbamate ring can be considered as a protecting group of the vicinal amino alcohol fragment, we conceived that 3 could provide a reliable access to iminosugar α- C -glycosides and then to N -substituted-α- C -glycosides, in both the classical and sp 2 -iminosugar series, thereby offering opportunities for molecular diversity. As a proof of concept, here we report (a) an optimized synthesis of 3 on a gram scale, (b) its transformation into NJ α- C -glycosides ( I ) by allylation–carbamate hydrolysis–cross-metathesis sequences, (c) the synthesis of N -alkyl ( II ) and N -( N’ -alkylthiocarbamoyl) ( III ) biantennary derivatives via an intermolecular reductive amination or a thiourea-forming reaction, respectively, and (d) the cyclization of the last two species to access bicyclic isothiourea analogues ( IV ; Figure , right panel).…”