D. Matthew G. Tilbrook

Investigations into the Chemistry of Some 1,6-Epithio and 1,6-Episeleno ß-D-Glucopyranoses

Derivatives of 1,6-dideoxy-1,6-epithio-β-D-glucopyranose have been shown to undergo oxidation reactions to afford the corresponding sulfoxides and sulfones. The sulfoxides participate in Pummerer reactions to afford the corresponding α-acetoxy sulfides which were then oxidized further. None of the sulfoxides, sulfones or α-acetoxy sulfides prepared were particularly efficient glycosyl donors. Also presented are crystal structures of 1,6-dideoxy-1,6-epithio-β-D-glucopyranose S,S-dioxide and 1,6-dideoxy-1,6-episeleno-β-D-glucopyranose, interesting analogues of 1,6-anhydro-β-D-glucopyranose.

An Improved Synthesis of (R)-2,3-Dihydroxypropyl 5-Deoxy-5-dimethylarsinyl-b--D-riboside, a Common Marine Arsenical

An efficient synthesis of (R)-2,3-dihydroxypropyl 5-deoxy-5-dimethylarsinyl-β-D-riboside, a common marine arsenical, from D-ribose, (S)-2,3-dibenzyloxypropanol and iododimethylarsine is described.

A New Catalyst for the Reductive Elimination of Acylated Glycosyl Bromides to Form Glycals

Ethylene-N,N-bis(salicylideneiminato)oxovanadium(IV) {VO(salen)} has been developed as a useful catalyst for the reductive elimination of acylated glycosyl bromides to form glycals, both in the pyranose and furanose series, using zinc/ammonium chloride/methanol or zinc/acetic acid/acetonitrile.

Some Approaches to Glycosylated Versions of Methyl β-Acarviosin

In a first approach to a glycosylated version of ‘methyl β-acarviosin’, a putative inhibitor of cellulases, cellobiose was converted into a carbocyclic enone that could not be transformed into the required amine for a subsequent alkylation. Alternatively, methyl β-acarviosin itself was glycosylated at C4′, using a ‘glycosynthase’, to provide the ‘trisaccharide’ (and some ‘tetrasaccharide’). Both of these molecules were effective inhibitors of various cellulases. In a related approach to a regioisomer of the above ‘trisaccharide’, a selectively protected derivative of 1-epivalienamine was alkylated with a carbohydrate triflate to give a ‘disaccharide’ that could not be glycosylated to give the desired ‘trisaccharide’. Another unsuccessful approach to this molecule is also reported.

An Investigation into the Synthesis of Some Molecules Related to Methyl Acarviosin

Methyl acarviosin is an impressive inhibitor of some glycoside hydrolases that process substrates containing α-D-glucosidic linkages. In an attempt to provide putative inhibitors for enzymes that process β-D-glucosidic linkages, we report an improved synthesis of a hydroxylated ‘methyl β-acarviosin’ and our efforts towards various deoxygenated versions of methyl β-acarviosin. As well, the synthesis of a 1,3-linked variant of methyl β-acarviosin is reported, together with an unsuccessful ‘tether’ approach to construct the crucial nitrogen linkage in the acarviosins.

The role of hydrolases in a synthesis of some epoxyalkyl β-C-cellobiosides

Abstract An endoglucanase from Humicola insolens has been used to glycosylate a range of alkenyl β- d -C- glucopyranosides with β-lactosyl fluoride. The resulting trisaccharides have been subjected to the action of a commercial β-galactosidase to form alkenyl β-C-cellobiosides. Oxidation of these has given a range of epoxyalkyl β-C-cellobiosides, putative inhibitors of cellobiohydrolases.

The Synthesis of a Diastereoisomer of Methyl Acarviosin

In model studies, a fully protected D-galactopyranoside 4-triflate and two 6-deoxy analogues were shown to alkylate cyclohexylamine, leading to 4-cyclohexylamino-4-deoxy- and 4,6-dideoxy-D-glucopyranosides as the major products in satisfactory yield, accompanied by alkenes resulting from elimination of triflic acid. Coupling of tetra-O-benzyl-1-epivalienamine with methyl 3-O-benzoyl-6-deoxy-4-O- trifluoromethylsulfonyl-β-D-galactoside gave a diastereoisomer of methyl acarviosin in protected form. Deprotection completed the first synthesis of methyl 4,6-dideoxy-4-[(1′R,4′R,5′S,6′S)-4′,5′,6′-trihydroxy-3′-(hydroxymethyl)cyclohex-2′-enyl]amino-β-D-glucoside, a potential β-glycosidase inhibitor.