title: Synthesis of a biologically active isomer of kotalanol, a naturally occurring glucosidase inhibitor.
abstract: The syntheses of an isomer of kotalanol, a naturally occurring glucosidase inhibitor, and of kotalanol itself are described. The target compounds were synthesized by nucleophilic attack of PMB-protected 1,4-anhydro-4-thio-d-arabinitol at the least hindered carbon atom of two 1,3-cyclic sulfates, which were synthesized from d-mannose. Methoxymethyl ether and isopropylidene were chosen as protecting groups. The latter group was critical to ensure the facile deprotection of the coupled products in a one-step sequence to yield kotalanol and its isomer. The stereoisomer of kotalanol, with the opposite stereochemistry at the C-6' stereogenic centre, inhibited the N-terminal catalytic domain of intestinal human maltase glucoamylase (ntMGAM) with a K(i) value of 0.20+/-0.02microM; this compares to a K(i) value for kotalanol of 0.19+/-0.03microM. The results indicate that the configuration at C-6' is inconsequential for inhibitory activity against this enzyme.
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
authors.forename: Razieh
authors.initials: R
authors.lastname: Eskandari
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Jayakanthan
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Kuntz
authors.forename: David R
authors.initials: DR
authors.lastname: Rose
authors.forename: B Mario
authors.initials: BM
authors.lastname: Pinto
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007536:Isomerism; D008358:Mannose / Q000737:chemistry; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013431:Sulfates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; C114502:Kotalanol; D009005:Monosaccharides; D013431:Sulfates; D000520:alpha-Glucosidases; D008358:Mannose