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

2,5-Anhydroglucitul and 2,5-anhydromannitol and their 6-phosphate and 1,6-d iphosphate derivatives are cyclic analogues of the alpha and beta anomers o f D-fructofuranose, D-fructofuranose-6-phosphate, and D-fructofuranose-1,6- diphosphate. They were synthesized from protected D-mannose or D-glucose. T he synthetic method was developed with emphasis on selective H-2 labeling o f these compounds, as a model for H-3 incorporation, which will be used for further biochemical studies. A key cyclization step, based on a benzyl eth er 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 wer e obtained from the same intermediate by changing the sequence of deprotect ion and phosphorylation steps.