Development of methods for a 2-carbon extension of fatty acids under mild conditions

Opara, Ugonna

Abstract

Polyunsaturated fatty acids (PUFAs) play important roles in the human body in preventing and treating diverse diseases which includes Alzheimer's disease, cancers, cardiovascular diseases, epilepsy, inflammatory diseases and many others. Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) sourced from marine fish are beneficial for vision and brain development. However, polyunsaturated fatty acids cannot be synthesized by the body and are obtained from dietary sources such as fish oils, nuts, seeds and dairy products. Extending the chain of polyunsaturated fatty acids by 2 carbons results in rare lipids for biological evaluation, which cannot be obtained in large quantities from plant and animal sources and is therefore the aim of this study.
The objective was to develop methods of a 2-carbon chain elongation of the polyunsaturated fatty acids under mild conditions using Meldrum’s acid under basic conditions. Furthermore, ring opening of the Meldrum’s acid under different reaction conditions led to the synthesis of the esters of the 2-carbon extended fatty acids.
The optimisations were first investigated using a model compound, 4-methoxyphenylacetic acid, which were then employed to the fatty acids of interest. 4-methoxyphenylacetic acid in the acylation and reduction steps with carbonyldiimidazole obtained a yield of 54% and ethyl ester yield of 49%. The esterification of the fatty acids occurred under acid-free (basic) conditions and shorter reaction times. The 5-alkyl Meldrum’s acid derivatives of oleic acid and dihomo--linolenic acid yielded very low quantities of 2% and 7% respectively. Nevertheless, the longer chain fatty acids did not yield desired results which could be attributed to non-enzymatic oxidation.
In conclusion, rare lipids were synthesized in a 3-step reaction under basic conditions and shorter reaction time with Meldrum’s acid as a precursor and a coupling agent, but antioxidants are necessary for longer chain fatty acids to prevent oxidative degradation.

Citation

Opara, U. (2025). Development of methods for a 2-carbon extension of fatty acids under mild conditions. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/5086194

• Thesis Type: Thesis
• Deposit Date: Mar 20, 2025
• Publicly Available Date: Jan 8, 2030
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/5086194
• Additional Information: School of Natural Sciences; University of Hull
• Award Date: Jan 7, 2025