Microwave-Assisted Synthesis And Application Of β-C-Glycosidic Ketones

C-Glycosides are being used as building blocks for the synthesis of a variety of biologically important natural products and synthetic compounds. The interest in C-glycosides lies on the stability of the C-glycosidic linkage, which is resistant to both enzymatic and chemical hydrolysis. However, stereoselective synthesis of C-glycosides has been a challenging task for organic chemists.The previous conventional methodologies for the synthesis of aryl ketone β-C-glycosides have some obvious defects, including long reaction time (12h), low yields (6-64%), and so on. As a result, we need faster and more efficient methods for the synthesis of aryl ketone β-C-glycosides.This paper described a detailed optimization procedure for the microwave-assisted stereoselective synthesis of aryl ketone β-C-glycoside in D-glucose case and investigated the scope of this methodology for the preparation of several C-glycoside derivatives. This one-step protocol involved Knoevenagel condensation between unprotected aldoses and dibenzoylmethane catalyzed by NaHCO3in the co-solvents EtOH-H2O (4:1, V/V) under400W microwave irradiation, which gave aryl ketone β-C-glycosides with higher yields (99%with C-glucoside,98%with C-mannoside) and better anomeric selectivities (β-configuration>95%) in a shorter reaction time (90min), compared with previous conventional methodologies.Using this method, partially protected aryl ketone β-C-glycosides and its derivatives3-acetamido-3-deoxy-β-C-glycosidic ketones were synthesized from the corresponding partially protected aldoses and aminosugars. This methodology provided an attractive alternative to the existing means for the regioselective protection of C-glycoside2-or3-hydroxyl group, and avoided the epimerization and anomerization.Regioselective tosylation of2,3-hydroxyl groups for2-C-(4’,6’-O-benzylidene-P-D-glucopyranosyl)-acetone,2-C-(4’,6’-O-benzylidene-β-D-glucopyranosyl)-acetophenone and2-C-(4’,6’-O-benzylidene-β-D-glucopyranosyl)-ethylbenzene were investigated detailedly. Compared with O-glycosides, it was very difficult to protect2-or3-hydroxyl group of C-glycosides selectively, because C-glycosides had no anomeric effect.3-Acetamido-3-deoxy-β-C-glycosidic ketone was synthesized from the nucleophilic substitution of3-tosyl product.Based on the above methodologies, β-C-glycosidic aminosugars, β-glucosidase inhibitors a-bromoacetone-β-C-glycosides and the potential drug for the treatment of cardiovascular disease β-C-glycosidic nitrates were synthesized, which have good application prospects in organic chemistry, biochemistry, medicinal chemistry and asymmetric catalysis.β-C-Glycosidic aminosugars were synthesized through selective nucleophilic ring-opening reaction of2,3-anhydro-β-C-glycosides with good yields (37-97%). a-Bromoacetone-β-C-glycosides were synthesized concisely from cheap and available aldoses, by the two reactions of C-glycosylation and a-bromination using1,3-Dibromo-5,5-Dimethylhydantoin (DBDMH) as an efficient and environment-friendly brominating agent. The overall yield was twice as many as that of the previous literature reported. β-C-glycosidic nitrates were synthesized from β-C-glycosidic ketones, through selective protection of the4,6-position hydroxyl of pyranose ring and nitration using fuming nitric acid in acetic anhydride, which were new candidate compounds for new drug development and structure-activity relationship study.