Synthesis Of Iminosugars Research Articles

Stable Ditriflates of D‐Glucose in the Synthesis of Iminosugars and Polyhydroxylated Pipecolic Acids

AbstractA synthesis of the five membered iminosugar DAB and a divergent synthesis of the six membered iminosugar 1‐dehydromannojirimycin (DMJ) and the corresponding sugar imino acid are reported. They involve double nucleophilic displacements of a D‐xylose ditriflate by benzyl carbazate and a D‐glucose ditriflate by allyl amine, respectively. They are followed by a similar protocol consisting of hydrolysis and oxidation or reduction of the resulting bicyclic glycosides. This allowed DMJ to be obtained from the cheap sugar D‐glucose.

Three-Component Reaction of Sugar Hydroxylactone, Amine and Isocyanide for the Synthesis of Iminosugars

Three-Component Reaction of Sugar Hydroxylactone, Amine and Isocyanide for the Synthesis of Iminosugars

Iminosugars Spiro-Linked with Morpholine-Fused 1,2,3-Triazole: Synthesis, Conformational Analysis, Glycosidase Inhibitory Activity, Antifungal Assay, and Docking Studies.

Synthesis of iminosugars 1, 2, 3a, and 4a and N-alkyl (ethyl, butyl, hexyl, octyl, decyl, and dodecyl) derivatives 3b–g and 4b–g spiro-linked with morpholine-fused 1,2,3-triazole is described. Conformation of the piperidine ring in each spiro-iminosugar was evaluated by 1H NMR spectroscopy, and conformational change in N-alkylated compounds 4b–g with respect to parent spiro-iminosugar 4a is supported by density functional theory calculations. Out of 16 new spiro-iminosugars, the spiro-iminosugars 3a (IC50 = 0.075 μM) and 4a (IC50 = 0.036 μM) were found to be more potent inhibitors of α-glucosidase than the marketed drug miglitol (IC50 = 0.100 μM). In addition, 3a (minimum inhibition concentration (MIC) = 0.85 μM) and 4a (MIC = 0.025 μM) showed more potent antifungal activity against Candida albicans than antifungal drug amphotericin b (MIC = 1.25 μM). In few cases, the N-alkyl derivatives showed increase of α-glucosidase inhibition and enhancement of antifungal activity compare to the respective parent iminosugar. The biological activities were further substantiated by molecular docking studies.

Allylic Azide Rearrangement in Tandem with Huisgen Cycloaddition for Stereoselective Annulation: Synthesis of C-Glycosyl Iminosugars.

Allylic azide rearrangement is used in tandem with intramolecular azide-alkene cycloaddition to give a triazoline that when subsequently decomposed in the presence of a nucleophile gives piperidines. The tandem reaction gives two stereocenters that are generated with high control. The formation of the piperidines required the presence of innate conformational constraint. The applicability of the annulation reaction is demonstrated by the synthesis of iminosugars. A proposal is included to account for the observed stereoselectivity, which is influenced by the precursor structure.

ChemInform Abstract: Synthesis of Iminosugars from Tetroses.

ChemInform Abstract: Synthesis of Iminosugars from Tetroses.

Synthesis of Iminosugars from Tetroses

Iminosugars continue receiving a great deal of attention from chemists and biochemists for their potential as pharmaceutics. This is a comprehensive review of the methods found in the literature for the synthesis of piperidine, pyrrolidine, indolizidine, and pirrolizidine iminosugars, starting from D/L-erythrose and D/L-threose carbon chains (tetroses). This review shows the crescent popularity of small molecules to build up iminosugar molecules. Methodologies described herein utilize inexpensive commercial materials. The synthesis of the four tetroses is included referring old and modern methodologies. Keywords: Erythose, indolizidines, piperidines, pyrrolidines, pyrrolizidines, threose.

An approach to 8 stereoisomers of homonojirimycin from d-glucose via kinetic & thermodynamic azido-γ-lactones

Crystal structures were obtained for the two C2 epimeric azido-γ-lactones 2-azido-2-deoxy-3,5:6,7-di-O-isopropylidene-d-glycero-d-ido-heptono-1,4-lactone and 2-azido-2-deoxy-3,5:6,7-di-O-isopropylidene-d-glycero-d-gulo-heptono-1,4-lactone prepared from kinetic and thermodynamic azide displacements of a triflate derived from d-glucoheptonolactone. Azido-γ-lactones are very useful intermediates in the synthesis of iminosugars and polyhydroxylated amino acids. In this study two epimeric azido-heptitols allow biotechnological transformations via Izumoring techniques to 8 of the 16 possible homonojirimycin analogues, 5 of which were isolated pure because of the lack of stereoselectivity of the final reductive amination. A side-by-side glycosidase inhibition profile of 11 of the possible 16 HNJ stereoisomers derived from d-glucose and d-mannose is presented.

Synthesis of iminosugars via 1,3-dipolar cycloaddition reactions of nitrones to α,β-unsaturated sugar aldonolactones

Abstract 1,3-Dipolar cycloaddition reactions of nitrones to α,β-unsaturated γ- and δ-lactones are presented. The special emphasis is placed on cycloadditions involving five-membered nitrones. Contrary to the additions involving δ-lactones, where only the exo approach of reactants is observed providing in many cases a single product, γ-lactones can add five-membered ring nitrones in both exo and endo mode. Moreover, in the case of γ-lactones, upon heating and prolongation of the reaction time, visible reversibility of the reaction is observed and, as the consequence, the formation of more stable, thermodynamic products is noticed. The energies of the 1,3-dipolar cycloaddition of cyclic nitrones with α,β-unsaturated lactones have been investigated through molecular orbital calculations to reproduce well the observed experimental facts. The usefulness of adducts obtained via cycloaddition reactions to the iminosugars synthesis is demonstrated by a large number of examples, since both components usually offer good regio- and stereoselectivity with the introduction of convenient functionalities. The strategy involves hydrogenolysis of the N–O bond followed by the construction of the desired iminosugar skeleton via intramolecular alkylation of the nitrogen atom.

Synthesis of 1,4-dideoxy-1,4-iminoheptitol and 1,5-dideoxy-1,5-iminooctitols from d-xylose

The synthesis of iminosugars from inexpensive d-xylose in high yields has been developed. The key step in this synthesis involves Wittig olefination or chelation-controlled attack of Grignard reagents on lactol and ring-closing metathesis using first or second generation Grubbs’ catalysts.

Synthesis of Iminosugars from α,β‐Unsaturated Lactones and N‐Benzyl Nitrone.

AbstractFor Abstract see ChemInform Abstract in Full Text.