The Kolbe Laboratory of Organic Synthesis (LKSO-FURG) develops methods for the synthesis of nitrogen and oxygenated organic compounds and studies their technological and/or pharmacological applications.
To study biodiesel synthesis, the transesterification reaction is observed in the presence of alcohols and vegetal oils (Figure 1). This work is being developed using the bench and pilot scales. The pilot plant demonstration consists of plant oil extraction and biodiesel production on a pilot scale of 200 kg/batch. Another project that receives financial support from Petrobras seeks to produce biodiesel from microalgae.
This group also studies the technological application of fatty compounds. One of its studies reported the synthesis of new N-acyl amino acids and N-acyl amino esters from fatty saturated and unsaturated acids derived from vegetal oils. The novel compound structures were based on the natural availability of the amino and fatty acids, which are biodegradable and naturally self-organize in organic solvents to form gels. The gel formation properties of 40 compounds were evaluated using n-hexane, toluene and gas (a complex mixture of hydrocarbons) as organic solvents (Figure 2).
Figure 2. Gels obtained in various compositions: (a) hexane and (b) toluene with 10mg of fatty acids derived from renewable sources.
These results have pharmacological applications. The introduction of fatty chains in organic molecules and the resulting increase in lipophilicity may cause significant and useful changes in their physical, chemical and biological properties. To investigate these properties, the LKSO pursues two lines of research: first, the development of methodologies for synthesizing new nitrogen molecules of pharmacological interest to produce structurally simple and inexpensive molecules. Second, increasing the lipophilicity of biologically active molecules by inserting fatty chains. These fatty molecules are obtained from the fatty acids of renewable sources, such as palmitic, stearic, oleic, ricinoleic, linoleic, linolenic and arachidonic acids. Several of this group’s studies have already demonstrated the antitubercular and antitumoral activities of fatty amides, and it may be possible to demonstrate the influence of fatty chains and the nitrogen portion of the molecules on this pharmacological activity. In one study on antitubercular activity, several fatty chains were inserted into an isoniazid molecule (the drug of choice in the treatment of tuberculosis). The result was a pronounced increase in the potency of the compound, especially against Mycobacterium tuberculosis-resistant isoniazid strains (Figure 3). Furthermore, fatty amides have been shown to be potent and selective against some tumor cell lines, including glioma lines (one of the most deadly forms of brain cancer). Several of this group’s studies have synthesized new heterocycles, such as dihydropyrimidinones and dihydropyridines—which have already been shown to be active against several tumor cell lines—through multicomponent reactions to verify the influence of the fatty chain in this activity. One study, in which the fatty chain was inserted into the GABA molecule (the major inhibitory neurotransmitter of the central nervous system) to increase its permeability against the blood-brain barrier, suggests that these compounds permeate this barrier by initiating a change in brain excitability. This may herald a promising treatment for CNS disorders such as epilepsy and migraine.
Figure 3. Antimycobacterial activity of isoionized derivatives from fatty acids from renewable sources.
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