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OPTIMIZATION OF THE ASTAXANTHINE ETER SYNTHESIS BY THE METHOD OF MATHEMATICAL PLANNING

DOI: https://doi.org/10.29296/25877313-2023-06-01
Issue: 
6
Year: 
2023

S.V. Pechinskii
Ph.D (Pharm.), Associate Professor, Department of Pharmaceutical Chemistry,
Pyatigorsk Medical Pharmaceutical Institute – Branch of Volgograd State Medical University (Pyatigorsk, Russia)
SPIN: 9798-4663; Researcher ID: AAN-3254-2020;
ORCID: 0000-0002-9505-9990; Scopus Author ID: 55993869200
E.T. Oganesyan
Dr.Sc. (Pharm.), Professor, Head of Department of Organic Chemistry,
Pyatigorsk Medical Pharmaceutical Institute – Branch of Volgograd State Medical University (Pyatigorsk, Russia)
SPIN: 7712-0253; Researcher ID: ABI-2824-2020;
ORCID: 0000-0002-2756-9382; Scopus Author ID: 9132988300
A. G. Kuregyan
Dr.Sc. (Pharm.), Professor, Department of Pharmaceutical Chemistry,
Pyatigorsk Medical Pharmaceutical Institute – Branch of Volgograd State Medical University (Pyatigorsk, Russia)
SPIN: 4547-1787; Researcher ID: AAN-3267-2020;
ORCID: 0000-0002-0698-8254; Scopus Author ID: 6506046751

Relevance. Astaxanthin occurs naturally in free and esterified form. An important distinguishing property of astaxanthin esters is their great stability during storage, heating and oxidation. It is possible to obtain a substance with an optimal set of physical, chemical and biological characteristics by improving the method of synthesis of the active molecule, which is rationally carried out by mathematical methods. The purpose of the study is to optimize the method for the synthesis of astaxanthin ester and benzoic acid by the method of mathematical planning of the experiment. Material and methods. The influence of the synthesis parameters on the yield of the ester of astaxanthin and benzoic acid, β,β-carotene-4,4'-dione-3,3'-dibenzoate, was evaluated by the method of mathematical planning of the experiment, using the construction of a mathematical model based on the first-order regression equation. Results. The steep ascent method was used to determine the optimal parameters for the synthesis of β,β-carotene-4,4'-dione-3,3'-dibenzoate. The maximum yield of the target product – β,β-carotene-4,4'-dione-3,3'-dibenzoate was achieved at a synthesis temperature of 60°C, a reaction time of 4.5 hours, a biocatalyst amount of 0.5 g, and a stirring speed of 55 rpm. Conclusions. Using the construction of a mathematical model and the search for optimal conditions using the steep climb method, we managed to increase the yield of the target synthesis product – β,β-carotene-4,4'-dione-3,3'-dibenzoate from 50% in the initial conditions to 65%, and also to reveal the influence of all considered factors on the synthesis process. The data obtained on the basis of the conducted studies by the method of mathematical planning of the experiment suggest that the optimal yield of β,β-carotene-4,4'-dione-3,3'-dibenzoate is achieved if the synthesis is carried out at 60°C for 4.5 hours, with a stirring speed of 55 rpm and in the presence of 0.5 g of the Novozyme 435 biocatalyst. During the experiment, it was found that an additional optimization parameter to be introduced into the model could be the “number of biocatalyst use cycles”. However, at the moment it cannot be taken into account in the mathematical model, because this property of the enzyme refers to uncontrolled optimization factors.
Keywords: 
mathematical design of experiment
steep ascent
astaxanthin
benzoic acid
biocatalysis
esterification.
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