Recently, many efforts have been made toward the efficiency in the natural product synthesis, and the more efficient stereocontrol as well as the shorter number of steps is required for that purpose. Herein, we report the detail of efficient total syntheses of three natural products using original methods for controlling the stereochemistries of ether rings. <Asymmetric synthesis of sniroacetal pheromone based on the substituent-indenendent stereocontrol at the spirocenter> Spiroacetal is one of the basic substructure in the bioactive natural products. Spiroacetalic natural products exhibit extensive biological function such as pheromonal, antibacterial and anticancer activities and so on. In the syntheses of these spiroacetals, their spirocenters are generally controlled by the stereochemical and/or electrochemical effect(s) of the substituent(s). However, stereocontrol of the spirocenter is sometimes difficult when effect(s) is(are) insufficient or when competitive effects exist. We developed a novel constructive method for the completely stereoselective synthesis of spiroacetals by using a stereochemical restriction of 4-membered-ring sulfide, and which provide the new synthetic approach to spiroacetalic compounds. Asymmetric dialkylation of SAMP-hydrazone (S)-4 prepared from 3-thietanone (3) gave compound 5. Optically pure (+)-olean was synthesized from 5 via acid treatment followed by desulfurization. Even the very unstable and non-anomeric compound 16 could also be synthesized by the same method from RANP-hydrazone (R)-4.<Asymmetric total synthesis of (+)-anthecularin> Anthecularin (19) was isolated from a lipophilic extract of the aerial parts of Greek Anthemis auriculata by Karioti and co-workers in 2006. This compound exhibits antitrypanosomal and antiplasmodial activity and inhibited two key enzymes of the plasmodial type II fatty acid biosynthesis pathway, PfFabI and PfFabG. Anthecularin has a characteristic structure with fused oxabicyclo[3.2.1]octene, cyclohexene and butyrolactone rings. Although four contiguous asymmetric centers exist in the molecule, only the relative stereochemistry has been clarified. Its unique structure prompted us to embark on the total synthesis. We achieved the total synthesis of anthecularin via the two ring closing metatheses as key reactions. The stereocontrolled addition of vinyllithium to 37a + 38a was achieved by the chelation effect of methoxyethoxy group. The overall yield was 7.9% over 18 steps, and the absolute configuration of anthecularin was determined to be 2S,3S,4R,8S by the comparison of the specific rotations between the natural and our synthetic sample.
