title: Synthesis of polyhydroxy 7- and N-alkyl-azepanes as potent glycosidase inhibitors.
abstract: An effective synthetic method for polyhydroxylated azepanes that contain an alkyl group (Me or Bu) at either the 7- or N-positions is developed. The synthetic routes are accomplished in eight to ten steps from d-(-)-quinic acid. Among the compounds synthesized, the polyhydroxy 7-butyl azepane (compound 3), which possessed the R-configuration at C-7 position, is shown to give potent inhibition against β-galactosidase (IC(50)= 3 microM). Preliminary biological data indicate that the length of alkyl groups along with the proper stereochemistry at the C-7 position is essential for acquiring extra binding affinity. Using similar synthetic routes, the polyhydroxy N-methyl and N-butyl azepanes are synthesized for the comparison of their biological activities.
authors.affiliation: Department of Chemistry, Tamkang University, Tamsui 25137, Taipei County, Taiwan. tlshih@mail.tku.edu.tw
authors.forename: Tzenge-Lien
authors.initials: TL
authors.lastname: Shih
authors.forename: Ming-Tsung
authors.initials: MT
authors.lastname: Liang
authors.forename: Kuen-Da
authors.initials: KD
authors.lastname: Wu
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lin
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011743:Pyrimidines; D006026:Glycoside Hydrolases