UNISP

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Synthesis of Analogues of Tyrosine and Peptides with Opioid Activity.

By

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                                                                                  Dr Jonas Kemkia

Chemical and pharmaceutical technologist at

the University of Ferrara -Italy  

Coordinator UNISP Reseach Program.

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The Chemistry of synthesis requires more patience, precision and a good knowledge of reagents because some chemical reactions are too difficult. That is why, we have to be rigorous and at the same time have a high manual capacity. A Lab technician is expected to get an advance capacity in innovation and creativity. He can also acquire and grow more of his leadership because he is civilly and criminally responsible of what happens and what he does. For instance, sometimes, during the manipulation we might be nervous and irritated; this often happens when our reactions tends to go bad. Synthesis of the same substance could be done using different, reducing thereby the repetition while helping in making the experiment more interesting. Another problem is the difficulty with respect to timeline. We can also be constrained to stay in laboratories for weekends.

Presented below is a more simplify abstract of my thesis.

 

 

 

 

                                                                                                       

 

 

 

 

 

 

 

 

 

 

 

 

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Objective: synthesis of a new drug with capable activities of reducing pain and inflammation (drugs with analgesic activity)

Key subject: Organic chemistry, pharmaceutical chemistry, toxicology, analytic chemistry, inorganic chemistry, method of synthesis and extraction of reactive agent.

Laboratory practice: different synthesis techniques, automatic peptide synthesis, analytic and preparative HPLC. Mass, NMR,

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Our research begins just after studies that confirmes that:

 

1-    The oppioids receptors are the only receptors that can be activated and interacting more with some endogen ligands calling oppioids ligands. This interaction is the basic principle of pain reduction ( chronic pain, inflammation, pain after surgery intervention)

 

2-     Lots of these endogen ligands have in their aminoacid sequence the tyrosine residue in the N-terminal. According to another research, the low bioavailability and duration of action of oppioid endogen is due to the tyrosine residue. In effect in the molecular structure of narcotic analgesic, the tyrosine similar part is responsible for the interaction in the receptor site calling “message domain”. The ossidrile group form hydrogen bonds, but it is also responsible for metabolism, conjugation and excretion.

According to this observation, we have:

 

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Bioisosterically substituted the tyrosine phenol with 2-aminobenzothiazole (2aba)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1-    Substitution of tyrosine present in position 1 of the oppioids ligands with a new molecular synthesized.

 

 

 

 

 

 

 

 

 

 

 

The synthesis results were satisfactory, we obtain best yield with the HPLC, MASS, and NMR, TLC and other purification technique have confirmed the purity of our substances.  These molecules are going to be tested pharmacologically. This table is an abstract of the  pharmacology hypothesis.