Synthesis of Coenzyme Q₁₀

Abstract

Problem statement: CoQ₁₀ is a key compound in ATP synthesis having wide number of health application especially for treating humans suffering from pathophysiological condition. The CoQ₁₀ presently available in the market is solely derived from fermentation process. A commercially viable synthetic process is yet to be realized. Approach: The researchers described a new synthetic route for the preparation of CoQ₁₀ (1). This new process utilized inexpensive isoprenol as a precursor for the synthesis of an early intermediate with a single isoprene unit. Another key step was the selective oxidation of trans methyl of isoprene unit as a prelude to the expansion of the side chain to decaprenyl group using solanesol. Results: Prenylation of 2, 3-dimethoxy-5-methylhydroquinone using isoprenol in presence of a Lewis acid, followed by selective oxidation of trans methyl group of isoprenyl side chain and subsequent allylic bromination yielded a bromide precursor (7). The p-toluenesulfination of the bromide followed by coupling with solanesyl bromide and de-p-toluenesulfination yielded dimethyl derivative of the CoQ₁₀-quinol. Finally CAN oxidation of dimethyl quinol followed by purification yielded CoQ₁₀ in 13% overall yield. Conclusion: The present process achieved CoQ₁₀ starting from a relatively inexpensive precursor. Further improvement in the coupling reaction between 8 and solanesyl bromide may lead to a better and viable synthetic process.