Design and synthesis of glycosidase inhibitor 5-amino-1,2,3,4-cyclohexanetetrol derivatives from (−)- vibo-quercitol

• Published in: Bioorganic & medicinal chemistry 2005-07, Vol.13 (13), p.4306-4314
• Main Authors: Ogawa, Seiichiro, Asada, Miwako, Ooki, Yoriko, Mori, Midori, Itoh, Masayoshi, Korenaga, Takashi
• Format: Article
• Language: English
• Subjects: alpha-L-Fucosidase - antagonists & inhibitors; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cattle; Coffee - enzymology; Cyclohexanes - chemical synthesis; Cyclohexanes - chemistry; Cyclohexanes - pharmacology; Drug Design; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Glycoside Hydrolases - antagonists & inhibitors; Hydrolases; Kidney - enzymology; Liver - enzymology; Molecular Structure; Prunus - enzymology; Structure-Activity Relationship
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2005.04.003

5-Amino-5-deoxy-1- O-methyl- l- talo-quercitol ( 5), an analogue of strong α-fucosidase inhibitor 5a-carba-fucopyranosylamine ( 3), was synthesized and shown to be a moderate α-fucosidase inhibitor. In continuation of development of bioactive inositol derivatives, a 1- O-methyl derivative of 5-amino-5-deoxy- l- talo-quercitol was designed and synthesized as an analogue of the strong α-fucosidase inhibitor, 5a-carba-α- l-fucopyranosylamine, the methyl branch being replaced with methoxyl, and demonstrated to be a moderate α-fucosidase inhibitor. The present approach provides a possible route to apply alkyl ethers of aminodeoxyinositols as hexopyranose mimics of biological interest.