Carbohydrate-derived spiroketals:: stereoselective synthesis of di-D-fructose dianhydrides

A one-pot synthesis of di-D-fructose dianhydrides (DFAs) having the 1,6,9,13-tetraoxadispiro[4.2.4.2]tetradecane and 1,7,10,15-tetraoxadispiro[5.2.5.2]hexadecane skeleton has been accomplished. The methodology relies on the ability of per-O-protected 1,2-O-isopropylidene beta-D-fructofuranose and beta-D-fructopyranose derivatives to undergo a tandem acetal cleavage-intermolecular glycosylation-intramolecular spiroketalization process by reaction with suitable acid promoters, such as boron trifluoride etherate or trifluoromethanesulfonic acid, in apolar organic solvents. Spirocyclization proceeds then under irreversible reaction conditions to give binary mixtures of di-D-fructofuranose (alpha,alpha and alpha,beta diastereomers) or di-D-fructopyranose 1,2':2,1' dianhydrides (beta,beta and alpha,beta), respectively, the stereochemical outcome being dependent on the non-participating or participating character of the protecting groups. Thus, benzylated and allylated derivatives afford, preferentially, the non-symmetric DFAs (alpha,beta), with diastereomeric excess up to 92%. In contrast, the use of participating benzoyl groups favours the C-2-symmetric diastereomer in both series. (C) 2004 Elsevier Ltd. All rights reserved.