Study On Semi-Chemosynthesis Technics Of Coenzyme Q₁₀

Coenzyme Q₁₀ is a vital human nutrient with extensive uses.It has very important physiological and pharmacological activities.Especially as we are having a deeper understanding of its physiological and pharmacological activities,coenzyme Q₁₀ becomes an important kind of pharmaceutical and health-care product.As one of the most effective anti-oxidation product, Coenzyme Q₁₀ is widely used in the cure of cardiovascular disease,hepatitis,cancer,AIDS etc and in the improvement of immunotherapy.And now the supply of it greatly falls short of demand. However,since its chemosynthesis is still a major challenge,a practical synthesis of COQ₁₀ has not yet been achieved.By now,there are only several countries that have the capability to produce in scale like Japan and Korea.Although there are many chemosynthetic methods for Coenzyme Q₁₀,there are still many shortcomings in technics.The expensive solanesol was not fully utilized and thus the cost was much higher than that of advanced procedure in foreign countries.Many scientific researchers still proceed with exploring an excellent synthetical route.In this paper,the author did some research with emphasis on the semi-chemosynthetic methods using natural solanesol extracted from tobacco as starting material.The author adopted two approaches to synthesize Coenzyme Q₁₀——the Straightforward method and the Extension method. In this dissertation,firstly,retro-synthetic analysis of Coenzyme Q₁₀ was accomplished;Secondly, synthetic routes of ring,side chains and coupling between ring and side chains were designed; Thirdly,effects of the key technical and reaction conditions were determined;Finally,some interesting reaction machanisms were studied.In route A,Coenzyme Q₁₀ was synthesized through four-step process employing natural solanesol extracted from tobacco as the starting material.The first step,solanesol reacting with PBr₃, gave solanesyl bromide.The second step,involving phase transfer catalytic reaction with ethyl acetoacetate,gave solanesylacetone.The third step,solanesylacetone reacting with vinyl-magnesium bromide,gave isodecaprenol.In the last,Coenzyme Q₁₀ was prepared through rearrangement coupling reaction with hydroquinone as the quinone core and isodecaprenol as the polyprenyl side chain.In route B,the author used the product obtained from the addition of sulfonyl to isoprene to synthesize trans-1-phenylsulfonyl-2-methyl-4-hydroxy-2-butene through acetolysis and saponification.Then this C5 hydroxy sulfone reacted with the quinone core,gave Coenzyme Q₁ analog(quinone containing the C5 allylic sulfone moiety).Next,this Coenzyme Q₁ analog,reacting with solanesyl bromide through coupling reaction,gave Coenzyme Q₁₀ analog.In the last, Coenzyme Q₁₀ was prepared by getting rid of unnecessary groups and oxidation procedure.By comparison with the original literature,many improvements were made on technology, production cost,operation and so on.Both of the two routines are Coenzyme Q₁₀ synthetical routes which have application value in industry.