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Proceeding Paper

Synthesis of a Hybrid Molecule Based on Biologically Active 5Z,9Z-Eicosadienoic Acid and Vanillin †

by
Elina Kh. Makarova
1,*,
Alexey A. Makarov
1,
Lilya U. Dzhemileva
2 and
Usein M. Dzhemilev
2
1
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russia
2
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russia
*
Author to whom correspondence should be addressed.
Presented at the 27th International Electronic Conference on Synthetic Organic Chemistry (ECSOC-27), 15–30 November 2023; Available online: https://ecsoc-27.sciforum.net/.
Chem. Proc. 2023, 14(1), 24; https://doi.org/10.3390/ecsoc-27-16170
Published: 15 November 2023

Abstract

:
A hybrid compound based on (5Z,9Z)-eicosa-5,9-dienoic acid and vanillin was synthesized in high yield (94%) using a new intermolecular cross-cyclomagnesiation reaction of aliphatic and O-containing 1,2-dienes catalyzed by Cp2TiCl2.

1. Introduction

Vanillin (4-hydroxy-3-methoxybenzaldehyde) isolated from orchids (Vanilla planifolia, V. pompona or V. tahitiensis) is attracting attention for several reasons. First, vanillin as a flavoring agent is used in the food, nutraceutical, and pharmaceutical industries. Secondly, vanillin has a simple chemical structure, which can simplify its synthesis to some extent. Third, vanillin has been shown to have various biological activities, such as antitumor, antioxidant, and antimicrobial properties [1,2]. In addition, vanillin exhibited a neuroprotective effect in an experimental model of Huntington’s disease and ischemia [3].
An analysis of the literature showed that vanillin derivatives also exhibit versatile biological activity. In the studies of Boiko Y. A., the analgesic and anti-inflammatory activity of vanillin and its derivatives was established, which is associated with the effect of these substances on the TRPA-1 and TRPV-1 ion channels [4]. Scipioni M. and colleagues synthesized a number of vanillin derivatives and simultaneously demonstrated that their antioxidant activity is similar to the reference antioxidant Trolox [5]. Vanillin derivatives have a high antioxidant potential and a protective effect against oxidative stress in neuroblastoma cells [6]. Li’s research group reported the synthesis of a number of dendrimers from vanillin that have antioxidant properties and protective effects on fatty acids, DNA, and lipoproteins [7]. Vanillin derivatives are also used as multipurpose drugs for the treatment of atopic dermatitis with positive pharmacokinetic and pharmacodynamic results. Mourtzinos and colleagues have shown that carboxylic acid, obtained by oxidation of vanillin, increases its antibacterial effect [8].
Given the high biomedical potential of vanillin derivatives, we put forward the idea of synthesizing a hybrid compound based on 5Z,9Z-eicosa-5,9-dienoic acid and vanillin. We have previously shown that (5Z,9Z)-eicosa-5,9-dienoic acid has a high inhibitory activity of topoisomerases I (hTop1) and II (hTop2α) in vitro [9,10].

2. Results and Discussion

Using the cross-molecular cyclomagnesiation reaction of trideca-1,2-diene 1 with 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran 2 with EtMgBr in the presence of a Cp2TiCl2 catalyst gave 2,5-dialkylidenemagnezacyclopentane 3. Acid hydrolysis of cyclomagnesiation product 3 and oxidation of the formed tetrahydropyranyl ether 5Z with the Jones reagent, 9Z-diene 4, leads to 5Z,9Z-eicosadienoic acid 5. The esterification reaction of (5Z,9Z)-eicosa-5,9-dienoic acid 5 with vanillin 6 was carried out in CH2Cl2 at 0 °C in the presence of 4-dimethylaminopyridine and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; as a result, the target product was obtained with a yield of 94% (Scheme 1).

3. Conclusions

Thus, we have synthesized a hybrid compound based on natural biologically active (5Z,9Z)-eicosa-5,9-dienoic acid and vanillin with high yield (94%), using a new reaction of intermolecular cross-cyclomagnesiation of aliphatic and O-containing 1,2-dienes catalyzed by Cp2TiCl2 at the key stage.

4. Experimental Procedure

4-formyl-3-methoxyphenyl (5Z,9Z)-icosa-5,9-dienoate (7). 1H NMR (400 MHz, CDCl3) δ: 0.90 (t, J = 6.6 Hz, 3H), 1.45–1.28 (m, 16H), 2.03–1.77 (m, 2H), 2.22–2.12 (m, 8H), 265–2.60 (m, 2H), 3.91 (s, 3H), 5.51–5.34 (m, 4H), 7.51–7.20 (m, 3H), 9.96 (s, 1H). 13C NMR (100.62 MHz, CDCl3) δ: 191.03, 171.23, 152.01, 145.08, 135.16, 130.72, 130.60, 128.90, 128.62, 124.75, 123.42, 110.79, 56.04, 33.35, 31.92, 29.74, 29.65, 29.57, 29.50, 29.35, 29.27, 29.03, 27.42, 27.30, 24.85, 22.69, 14.12. MS (MALDI-TOF), m/z: 442 [M]+. C28H42O4. Found (%): C 75.79; H 9.41.Calcd for C28H42O4 (%): C 75.98; H 9.56.

Author Contributions

Conceptualization, U.M.D. and L.U.D.; methodology, A.A.M.; validation, E.K.M., resources, E.K.M.; data curation, U.M.D.; writing—original draft preparation, E.K.M., A.A.M.; writing—review and editing, U.M.D. and L.U.D.; visualization, E.K.M.; supervision, U.M.D.; project administration, A.A.M.; funding acquisition, A.A.M. All authors have read and agreed to the published version of the manuscript.

Funding

This work was done within approved plans for research projects at the IPC RAS State Registration No. FMRS-2022-0075.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data are contained within the article.

Conflicts of Interest

The authors declare no conflict of interest.

References

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Scheme 1. Synthesis of a hybrid compound based on (5Z,9Z)-eicosa-5,9-dienoic acid and vanillin.
Scheme 1. Synthesis of a hybrid compound based on (5Z,9Z)-eicosa-5,9-dienoic acid and vanillin.
Chemproc 14 00024 sch001
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MDPI and ACS Style

Makarova, E.K.; Makarov, A.A.; Dzhemileva, L.U.; Dzhemilev, U.M. Synthesis of a Hybrid Molecule Based on Biologically Active 5Z,9Z-Eicosadienoic Acid and Vanillin. Chem. Proc. 2023, 14, 24. https://doi.org/10.3390/ecsoc-27-16170

AMA Style

Makarova EK, Makarov AA, Dzhemileva LU, Dzhemilev UM. Synthesis of a Hybrid Molecule Based on Biologically Active 5Z,9Z-Eicosadienoic Acid and Vanillin. Chemistry Proceedings. 2023; 14(1):24. https://doi.org/10.3390/ecsoc-27-16170

Chicago/Turabian Style

Makarova, Elina Kh., Alexey A. Makarov, Lilya U. Dzhemileva, and Usein M. Dzhemilev. 2023. "Synthesis of a Hybrid Molecule Based on Biologically Active 5Z,9Z-Eicosadienoic Acid and Vanillin" Chemistry Proceedings 14, no. 1: 24. https://doi.org/10.3390/ecsoc-27-16170

APA Style

Makarova, E. K., Makarov, A. A., Dzhemileva, L. U., & Dzhemilev, U. M. (2023). Synthesis of a Hybrid Molecule Based on Biologically Active 5Z,9Z-Eicosadienoic Acid and Vanillin. Chemistry Proceedings, 14(1), 24. https://doi.org/10.3390/ecsoc-27-16170

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