First Total Synthesis of 1-O-β-d-Glucopyranosyl-5-deoxyadenophorine and Its Aglycon Congener:  Determination of the Absolute Configuration

• Published in: Journal of organic chemistry Vol. 69; no. 5; pp. 1497 - 1503
• Main Authors: Felpin, François-Xavier, Boubekeur, Kamal, Lebreton, Jacques
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 05.03.2004; Amer Chemical Soc
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Carbohydrate Conformation; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemistry; Chemistry, Organic; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzymes and enzyme inhibitors; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Glucosamine - analogs & derivatives; Glucosamine - chemical synthesis; Glucosamine - chemistry; Glycoside Hydrolases - antagonists & inhibitors; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Hydrolases; Magnetic Resonance Spectroscopy; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; ASYMMETRIC-SYNTHESIS; RING-CLOSING METATHESIS; ORGANOMETALLIC REAGENTS; BIOSYNTHESIS; ALLYLATION; IMINOSUGARS; CHIRAL IMINES; ALKALOIDS; Enzyme; Nitrogen heterocycle; Aglycone; Enzyme inhibitor; Chiral compound; Imine; Aldehyde; Diastereoselectivity; Total synthesis; Allylation; Pyridine derivatives; Stereoselectivity; Glycosidases; Absolute configuration; Bicyclic compound; Epoxidation; Hydrolases; Glycoside; Chemical synthesis; Oxygen nitrogen heterocycle; Regioselectivity; Chemical coupling; Alkaloid; α-Glucosidase; Six membered ring; O-Glycosidases
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo035522m

The first total synthesis of the potent glycosidase inhibitors 1-O-β-d-glucopyranosyl-5-deoxyadenophorine and its aglycon congener is described in respectively 13 steps (9% overall yield) and 9 steps (29% overall yield) from (R)-Garner aldehyde. The synthesis takes advantage of several key reactions including a diastereoselective allylation of a chiral imine, a stereoselective epoxidation, and a glycoside coupling. In addition this study established unambiguously the absolute configuration of the natural products.