Synthesis of selectively labeled D-fructose and D-fructose phosphate analogues locked in the cyclic furanose form

2,5-Anhydroglucitol and 2,5-anhydromannitol and their 6-phosphate and 1,6-diphosphate derivatives are cyclic analogues of the alpha and beta anomers of D-fructofuranose, D-fructofuranose-6-phosphate, and D-fructofuranose-1,6-diphosphate. They were synthesized from protected D-mannose or D-glucose. The synthetic method was developed with emphasis on selective (2)H labeling of these compounds, as a model for (3)H incorporation, which will be used for further biochemical studies. A key cyclization step, based on a benzyl ether nucleophilic attack on an activated alcohol, constructed the ring system. The stereochemistry at C(2) (alpha/beta anomers) and at C(5) (D sugar) was controlled by selective epimerizations. Mono- and diphosphate analogues were obtained from the same intermediate by changing the sequence of deprotection and phosphorylation steps.