Coenzyme Q <sub> 10 </ Sub> Synthesis Of New Technology Research,

Coenzyme Q₁₀ , as one of the like-vitamins, plays an important role in physiological function and clinical use. In this thesis, first the retro-synthetic analysis of Coenzyme Q₁₀ was accomplished, then a synthesis route was designed using Coenzyme Qo, solanesol and 4-chloro-3-methyl-2-buten-1-ol acetate as the starting material with an overall yield of 56.1% and 50.4% based on Coenzyme Qo and solanesol respectively. The synthesis can be divided into three parts: synthesis of the ring, the side chain and the coupling between the ring and side chain.Synthesis of 2,5-dibenzyloxy-3,4-dimethoxy-6-bormo-toluene was carried out by two routes.(l)From Coenzyme Qo by hydrogenation, benzylation and bromination with an overall yield of 55.6%;(2)From Coenzyme Qo by bromination first, then hydr--ogenation and benzylation with an overall yield of 80.3%.Synthesis of the side chain was accomplished using "C5+C45" strategy. C5 building block is 4-chloro-3-methyl-2-buten-l-ol acetate, which is industrially available and C₄₅ building block is solanesol sulfone. (All-E)-3,7,11,15,19,23,27,31,35,37-decamethyl-5-sulfonyl-2( 6,10,14,18, 22, 26, 30, 34, 38-tetracontadecaen-l-ol was prepared by coupling of C5 and C45 building block in THF/DMF, catalyzed by potassium tert-tutoxide with a yield of 80%. Then decaprenol was obtained after desulfonylation using PdCl2(dppp) and LiBHEt3, with a yield of 94.4% and the less than 1% ratio of double bond migration.Coupling of the ring and the side chain was accomplished by use of cross-coupling reaction of Grignard reagent. Thus the precursor of Coenzyme Q₁₀ was synthesized by preparation of Grignard reagent, coupling with decaprenyl chloride, with a yield of 76.9% and 92.3% based on the ring and the side chain respectively. Finally Coenzyme Q₁₀ was obtained by removal of protecting group with lithium-amine and oxidation in 90.8% yield.In the thesis, 18 chemical compounds were synthesized and their structure was confirmed by ¹H-NMR.