A series of ester derivates, potential prodrugs, of the antiviral agent oseltamivir carboxylate (OTVC) has been attempted synthesized. The aim was to synthesize prodrugs with high affinity for proteins compared to OTVC and with a slower conversion to the carboxylate in contrast to the ethyl ester oseltamivir (OTV) which is the active substance of Tamiflu®. The approach to increase the binding was to esterify the active compound of (OTV), OTVC, with a ligand that carry a free carboxylic acid. Such a component will carry a negative charge in vivo and be somewhat hydrophobic, and should therefore bind to albumin. Most likely, the prodrug with increased protein binding will give fewer side effects than the mother compound, due to the fact that it is highly bound to albumin rendering the free concentration low. It is also possible that a passive targeting effect can be achieved. This is because there has been observed enhanced protein retention effect in infected tissue.
Both the acid of the ligands, and the amine group of OTVC had to be protected in this synthesis in order to avoid side reactions. The amine was first tried protected with isonicotinyl. However, this synthesis proved to be troublesome. Tert - bytylcarbonate was therefore chosen instead. As a protection group for the acid, trichloroethanol (TCE) was chosen.
OTV was hydrolyzed and the amine group was protected with tert – butylcarbonyl. The acid of the ligand was protected with TCE and esterified with the acid of the protected OTVC. Due to lack of time, a successful deprotection step was not achieved.
There have not been published structures of neither OTV nor OTVC based on x-ray crystallography. It was an aim of this thesis to grow crystals of these compounds, and obtain a structure based on x-ray. There were obtained crystals both structures, however, they were too small for reliable data to be obtained.