Studies of some intramolecular carbohydrate free radical reactions

Abstract

The work presented in this thesis comprises a study of some intramolecular radical reactions carried out using radicals generated on substituents of glucopyranose derivatives. In the first part to this work, the possibility of an intramolecular radical cyclisation leading to the formation of a macrocycle was investigated. Treatment of the bromide radical precursor 2-bromoethyl 2,3,4-tri-O-acetyl-6-O-allyl-β-D-glucopyranoside with tributyltin hydride resulted largely in direct reduction of the initial radical to give the ethyl glucoside. However, a single macrocyclic product, the result of 11-endo addition of the radical to the double bond, was also formed, albeit in low yield (≈13%; unoptimised). No evidence of migration of the anomeric hydrogen atom to the initial oxyethyl radical was found in either the products of the radical reaction above, or when the 2-bromoethyl glucoside tetraacetate was treated with tributyltin deuteride. In the second part to this work, a spiroglucoside was synthesised in good yield by the radical spirocyclisation of a 2,3-epoxybutyl glucoside. Such spiroketals occur as substructures of many natural compounds of pharmacological importance. Epoxidation of (Z)-4-hydroxybut-2-enyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside gave a separable mixture of the two epoxide isomers which were converted to their analogous epoxyiodide derivatives before treatment with tributyltin hydride. The radical reaction of one of the epoxyiodide isomers resulted in a mixture of all four possible spiroglucoside isomers, whereas the other gave a good yield (68%) of a single spiroglucoside isomer, 1,4-anhydro-3-deoxy-3-C-methyl-5,6,7,9-tetra-O-acetyl-β-D-erythro-L-ido-non-4-ulopyranose. The β-spiroglucoside was able to be converted to its more stable α-anomer by acid catalysed epimerisation in accord with known stereoelectronic effects. An NMR NOESY experiment allowed assignment of the stereochemistry at C-3 of the major spiro-compound. It is proposed that the difference in outcomes of the two radical reactions could be accounted for by a hydrogen bonding interaction in the radical intermediates between the hydroxyl groups, resulting from cleavage of the epoxide rings, and the pyranoid oxygen atoms. An unusual by-product of the radical reaction of both epoxyiodide isomers was the aldehyde 4-oxobutyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside.