Biological method for protection of 6‐position of sucrose and its use in synthesis of disaccharide high‐intensity sweetener

Abstract

A general method for protecting the 6 primary hydroxyl position of sucrose is described. It involves the production of glucose-6-acetate by fermentation of glucose using a strain of Bacillus megaterium followed by conversion to sucrose-6-acetate as a kinetic product using a specially selected fructosyl transferase producted by a newly isolated strain of Bacillus subtilis. The sucrose-6-acetate was found to be more lipophilic than expected, and this property aided its purification by chromatography. Pure sucrose-6-acetate may then be chlorinated and subsequently deacetylated to give the high-intensity sweetener 4,1',6'-trichlo-4,1',6'-trideoxygalactosucrose (sucralose) in high yields. This process involves fewer steps than are required for chemical synthesis using trityl chloride and acetic anhydride. Related intensely sweet molecules which were synthesized by similar methods included 4,1',6'-trichloro, 4,1',6'-trideoxy L-arabinosucrose, and 4,1',6'-trichloro-4,6,1',6'-tetradeoxy-galactosucrose. They were obtained from xylose and 6-deoxyglucose, respectively, via the intermediates xylsucrose and 6-deoxysucrose, formed by the reaction of the fructosyl transferase on the monosaccharide acceptors.