Background: Adenosine triphosphate (ATP) is the energy currency of the body; it takes
part in various and indispensable metabolic processes for the maintenance of cell homeostasis, degrading
to its hydrolysis product, adenosine diphosphate (ADP). Efficient ways to restore ATP are
therefore necessary in the cells. When the cell lacks energy due to ischemic conditions or high
ATP demand, phosphocreatine gives its phosphate group to ADP that converts to ATP, in a reaction
catalyzed by the enzyme creatine kinase. For this reason, phosphocreatine is utilized as a
pharmacological treatment in human diseases that involve a failure of the cellular energy, most notably
in coronary artery disease.
Objective: Commercially available phosphocreatine is currently synthesized using different methods,
each of one characterized by a rather low yield of the final product, probably due to the low
reactivity of the guanylating reagent. The aim of this work is to overcome the drawbacks of the
synthetic methods currently employed, devising a novel synthetic route to obtain phosphocreatine
and phosphocreatine prodrugs in higher yields and purity.
Method: To obtain a higher yield of the final product and a lower number of sub-products, this
method utilizes a new guanylating agent characterized by high reactivity, endowed with a protecting
group t-Boc on one of the two nitrogen atoms of the guanidinic function and a protected phosphate
on the other one; that compound is then conjugated with an opportune secondary amine. The
obtained product is cleaved first with acidic conditions to obtain the phosphocreatine prodrug
(phosphocreatine ethyl ester) and then with an enzymatic method to obtain the phosphocreatine.
Result: Have been obtained in good yield and purity as demonstrated by HPLC and mass spectrometry
Conclusion: This novel synthetic route permits to obtain the phosphocreatine molecule in higher
yield and purity compared to the methods currently employed with a combination of chemical and