title: A new method to synthesize creatine derivatives.
abstract: Creatine is an amino acid that has a pivotal role in energy metabolism of cells. Creatine acts as an "ATP shuttle", carrying ATP to the sites where it is utilized, through its reversible phosphorylation by creatine kinase. Moreover, the creatine-phosphocreatine system delays ATP depletion during anoxia or ischemia, thus exerting a neuroprotective role during those pathological conditions. Thus, its administration has been advocated as a treatment or prevention of several conditions involving the central nervous system. However, creatine crosses poorly the blood-brain barrier and the cell plasma membrane, thus its administration has but a limited effect. The use of more lipophilic creatine derivatives has thus been suggested. However, such a synthesis is complicated by the intrinsic characteristics of the creatine molecule that hardly reacts with other molecules and easily cyclizes to creatinine. We obtained amide derivatives from creatine starting from a new protected creatine molecule synthesized by us, the so-called (Boc)2-creatine. We used a temporary protection only on the creatine guanidine group while allowing a good reactivity on the carboxylic group. This temporary protection ensured efficient creatine dissolution in organic solvents and offered simultaneous protection of creatine toward intramolecular cyclization to creatinine. In this manner, it was possible to selectively conjugate molecules on the carboxylic group. The creatine guanidine group was easily released from the protection at the end of the reaction, thus obtaining the desired creatine derivative.
authors.affiliation: Department of Neuroscience, Ophthalmology, Genetics, Maternal-Infantile Sciences, University of Genova, Largo Paolo Daneo 3, 16132, Genoa, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Garbati
authors.forename: Annalisa
authors.initials: A
authors.lastname: Salis
authors.forename: Enrico
authors.initials: E
authors.lastname: Adriano
authors.forename: Andrea
authors.initials: A
authors.lastname: Galatini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Damonte
authors.forename: Maurizio
authors.initials: M
authors.lastname: Balestrino
authors.forename: Enrico
authors.initials: E
authors.lastname: Millo
mesh_terms: D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D003401:Creatine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
chemical_list: D003401:Creatine