title: Regioselective opening of myo-inositol orthoesters: mechanism and synthetic utility.
abstract: Acid hydrolysis of myo-inositol 1,3,5-orthoesters, apart from orthoformates, exclusively affords the corresponding 2-O-acyl myo-inositol products via a 1,2-bridged five-membered ring dioxolanylium ion intermediate observed by NMR spectroscopy. These C-2-substituted inositol derivatives provide valuable precursors for rapid and highly efficient routes to 2-O-acyl inositol 1,3,4,5,6-pentakisphosphates and myo-inositol 1,3,4,5,6-pentakisphosphate with biologically interesting and anticancer properties. Deuterium incorporation into the α-methylene group of such alkyl ester products (2-O-C(O)CD2R), when the analogous alkyl orthoester is treated with deuterated acid, is established utilizing the novel orthoester myo-inositol 1,3,5-orthobutyrate as an example. Such deuterated ester products provide intermediates for deuterium-labeled synthetic analogues. Investigation into this selective formation of 2-O-ester products and the deuterium incorporation is presented with proposed mechanisms from NMR experiments.
authors: Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
authors: Himali Y
authors: HY
authors: Godage
authors: Andrew M
authors: AM
authors: Riley
authors: Timothy J
authors: TJ
authors: Woodman
authors: Mark P
authors: MP
authors: Thomas
authors: Mary F
authors: MF
authors: Mahon
authors: Barry V L
authors: BV
authors: Potter
mesh_terms: D000143:Acids / Q000737:chemistry; D002087:Butyrates / Q000138:chemical synthesis* / Q000737:chemistry; D004952:Esters; D006868:Hydrolysis; D007294:Inositol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
chemical_list: D000143:Acids; D002087:Butyrates; D004952:Esters; C584033:myo-inositol 1,3,5-orthobutyrate; D007294:Inositol