Preparazione di antiossidanti a struttura catecolica e di prodotti di interesse biologico di ossifunzionalizzazione benzilica da sostanze fenoliche naturali con sistemi biomimetici (IBX) ed enzimatici (laccasi/HBT)
Author(s)
Crisante, Fernanda
Date Issued
February 19, 2009
Type
Doctoral Thesis
Abstract
The research activity of this PhD course has developed oxidative methodologies by chemical and
enzymatic reagents to obtain fine-chemicals and high add-value molecules from natural phenols
present in agroindustrial wastes as starting materials.
A first aim has been the flavones methylation by using dimethyl carbonate (DMC) as
environmentally benign substitute for hazardous and toxic reagents such as methyl halides and
methyl sulfate. Reactions proceeded with complete substrate conversion and yield; final products
possess many biological and pharmacological activities.
Subsequently, DMC has been used as well as reagent for the selective carbomethoxylation of
aliphatic alcoholic chain of phenols and solvent for the selective acylation of these compounds.
Two methodologies of acylation have been developed; the first, by acetic anhydride in the presence
of a catalytic amount of RuCl3 as catalyst and the second, by acetyl chloride in DMC without any
catalyst. This simple and cheap last procedure has been extended to the esterification of these
compounds by using acyl chlorides with long saturated or unsaturated chains. All corresponding
products were obtained in satisfactory conversions and yields. Between the obtained compounds,
lipophilic derivatives of hydroxytyrosol are of particular interest.
Important results have been obtained by using hypervalent iodine reagents of oxidation as the 2-
iodobenzoic acid (IBX) and Dess-Martin Reagent (DMP). First, two convenient synthetic strategies
to prepare hydroxytyrosol as well its lipophilic derivatives have been developed from commercially
available, cheap natural phenols such as tyrosol and homovanillyl alcohol. These syntheses, for
their originality, simplicity, economic validity, efficiency and ecofriendly character, have been
deposited for a national and an international patent.
Hydroxytyrosol synthesis has been employed also to verify the efficiency of polymer-supported
IBX through the oxidative insertion of a hydroxyl and the demethylation reactions of phenolic
compounds. After the first oxidation, the polymeric reagent was recovered, regenerated and reused
for ten oxidation reactions without lack of efficiency to give the final products in excellent yields
achieving economic and environmentally benefits.
Other important molecules have been synthesized by using the oxidative chemistry of IBX:
piceatannol and its lipophilic derivates starting to trans-resveratrol; antioxidant flavones and
flavanones with catecholic structure; polyhydroxylated 1-arilisochromans. Again, we have applied
IBX for the dehydrogenation of carbonylic groups to synthesize flavones starting to flavanones and
for the oxidation of benzylic position of 1-arylisochromans to obtain fine-chemicals.
Finally, the chemistry of enzymatic catalytic system O2/laccases/HBT has been optimized to
oxidize benzyl ethereal position of 1-arylisochromans and benzylic position of catechins. Results
have been satisfactory; the catalytic system has been selective and efficient to insert an oxygen
atom in C-4 position miming the natural oxidation performed by bacteria contained in tea plants.
Additional information
Dottorato di ricerca in scienze ambientali
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