Chemical Synthesis of Ketopentose-5-phosphates

A chemical synthesis of ketopentose-5-phosphates that are involved in the pentose phosphate pathway has been developed. The ketopentose phosphates, D-ribulose-5-phosphate and D-xylulose-5-phosphate, were prepared in five steps starting from known intermediates. Starting from readily available D-aldopentoses, reduction of the corresponding furanose derivatives gave key intermediates in the form of aldopentitols. Selective phosphorylation, oxidation, and deprotection provided the target molecules. This chemical synthesis makes such ketopentose phosphates readily available, and as a result they could be used as assay substrates for mechanistic studies. Since the pentose phosphate pathway is important in cancer-cell metabolism, this synthetic approach provides an opportunity for preparing potential enzymatic inhibitors for use in drug development. To further extend this synthetic approach, a different protecting group (a trityl group) was used for the synthesis of the two parent ketopentoses (D-ribulose and D-xylulose) in a similar manner.