1.Studies On Asymmetric Total Synthesis Of （+）-biotin And Related Reaction 2.Studies On The High Stereoselective Synthesis Of Coenzyme Q₁₀

In this thesis, we have developed two high stereo- and region-selective total synthesis of （+）-biotin and coenzyme Q₁₀.In chapter 1, the development of Roche’s Sternbach total synthesis of （+）-biotin over the past six decades have been reviewed, including: 1) the preparation of the key chirl building block-（3aS, 6aR）-lactone; 2) the conversion of （3aS, 6aR）-lactone into （3aS, 6aR） - thiolactone; 3) the introduction on C₄ position of （3aS, 6aR） - thiolactone; 4) the Debenzylation of （+）-debenzylbiotin. As mentioned, the high stereoselective synthesis of （3aS, 6aR）-lactone and the convenient installation of carboxybutyl chain is still a challenge along the significant progress of Roche’s Sternbach total synthesis of （+）-biotin.In chapter 2, the modifications of C₆ and C₉ -position in Cinchona Alkaloids （quinine and quinidine） have been made to lead to the identification of 16 Cinchona derivatives for our asymmetric alcholysis of meso-cyclic anhydride in the total synthesis of （+）-biotin as organocatalysts. The different conditions, such as solvents, temperature, ratios of catalysts and alchols were investigated, the optimized reaction will aim to the high enantioselectivity preparation of （3aS, 6aR）-lactone, a key chiral intermediate for the total synthesis of （+）-biotin. An improved Fukuyama-type cross coupling reaction employing palladium nanoparticles immobilized anion exchang resin D296 （Pd@D296） was used in a one-step introduction of carboxybutyl chain onto （3aS, 6aR） - thiolactone. The third chiral center of （+）-biotin was established creatively by an ionic hydrogenation of 9 under mild reaction conditions. These promising results pave a way for exploring a practical and high steroselectivty total synthesis of （+）-biotin.In chapter 3, a view showing the considerable efforts toward the chemical synthesis of Coenzyme Q₁₀ from the first synthesis in 1959 is presented, including the strategies based on direct elaboration of decaprenyl side chain, the elongation of polyprenyl side chain and the total synthesis. The construction of liner polyprenoid chains represents a major synthetic challenge and the development of a convenient approach for the chemical synthesis of Coenzyme Q₁₀ is still in demand.In chapter 4, An improved route to coenzyme Q₁₀ via the C₅+C₄₅ approach starting from commercially available coenzyme Q₁ and solanesol was investigated, the key steps in this synthesis are the SeO₂-mediated oxidation of the protected isoprenylhydroquinone into the terminal trans-allylic alcohol without the formation of undesired stereoisomer and one-pot reductive elimination of the phenylsulfonyl and dibenzyl groups using lithium naphthalenide. In addition, another route to coenzyme Q₁₀ based on the C₀+C₅₀ strategy employing all-trans-decaprenyl alcohol and 4-hydroxy-2,3-dimethoxy-6-Methylphenyl acetate（4） has been developed. These research results provide good foundation for exploring the synthesis of natural products in possession of liner polyprenoid chains.The structure of all synthesized compounds were charactered by IR、¹H NMR、¹³C NMR、MS、CD, the absolute configuration of some now compounds were futher comfirmed by X-ray crystal structure analysis respectively.