In this dissertation,two natural products—(+)-biotin and(-)-reserpine were chosed as target molecule of total synthesis.In chapter 1,the siginificant progress of Roche's Sternbach total synthesis of (+)-biotin over the past 60 years has been reviewed,including:1) the synthesis of the key chiral building block—(3aS,6aR)-lactone,2) the conversion of(3aS,6aR)-lactone into(3aS,6aR)-thiolactone,3) the introduction of carboxybutyl chain on(3aS, 6aR)-thiolactone,4) debenzylation of(+)-dibenzylbiotin.In addition,the further improvements of the Sternbach approach are still the development of a high efficient synthesis of(3aS,6aR)-lactone and a short installation of carboxybutyl side chain.In chapter 2,the quinine-mediated asymmetric ring opening of meso-cyclic anhydride into chiral hemiesters was investigated.The different conditions of these asymmetric alcoholysis,such as different nucleophile(alcohols),solvent,ratio of reactants and temperature were optimized with the aim to prepare the chiral hemiesters in good yields with high enantioselectivity.A one-pot chemoselective reduction and lactonization of(4S,5R)-hemiesters was carried out to afford high-yielding(3aS,6aR)-lactone,a key chiral building block for the biotin synthesis. One-step introduction of carboxybutyl chain onto(3aS,6aR)-thiolactone was reached upon treatment of zinc reagent 25 in the presence of nanopalladium(LDH-Pd°) via an improved Fukuyama coupling under mild reaction conditions.The establishment of the third chiral center of(+)-biotin was done by an ionic hydrogenation of 26 with Et_3SiH and TFA at room temperature.On the other hand,we improved the preparation of the cyclic anhydride and(3aS,6aR)-thiolactone,and the debenzylation of (+)-dibenzylbiotin.These research works provided good foundation for exploring a practical and high efficient total synthesis of(+)-boitin.In chapter 3,the advances in total synthesis of(-)-reserpine during the past 50 years was reviewed.To date,eleven successful total syntheses of(-)-reserpine have been accomplished,and these synheses can be divided into E-ring and DE-ring strategy.Constructing the complex E-ring system by utilizing natural product as chiral pool and then coupling the E-ring synthon with tryptophyl unit undoubtedly constitutes a practical and efficient total synthesis of(-)-reserpine.In chapter 4,an efficient and chiron approach toward polysubstituted octahydrobenzofuran,an important(-)-reserpine E-ring analogue with five chiral centers is described using the easily available(-)-shikimic acid as chiral pool.The pivotal reactions include a Luch reduction,as well as an intramolecular radical cyclization,which allowed for the introduction of two chiral centers and two-carbon sidearm of E-ring in a single step.The primary results of this research provided a good chemical foundations for the total synthesis of(-)-reserpine.