1. Studies On Asymmetric Synthesis Of HMG-CoA Reductase Inhibitor And Related Reactions 2. Synthesis Of Katsube Nitrile:the Key Building Block For Eburnamine-Vincamine Alkaloids

This thesis mainly focused on the synthesis of statins including atorvastatin calcium (2-1) and rosuvastatin calcium (3-1) via anhydride desymmetrization and Keck asymmetric allylation strategies. In addition, synthesis of Katsube nitrile, a key building block for eburnamine-vincamine alkaloids, was also finished by using Pictet-Spengler cyclization. The details are summarized below:In chapter 1, the significant progress of synthesis of two chiral side-chain has been briefly reviewed. The chiral pool synthesis via (S)-epichlorohydrin was still an efficient industrial process.In chapter 2, asymmetric synthesis of atorvastatin calcium (2-1) via bifunctional sulfonamide catalytic anhydride desymmetrization was investigated starting from diethyl 3-hydroxyglutarate in an overall yield of 18%. The organocatalytic enantioselective desymmetrization of 7 by alcoholysis employing bifunctional sulfonamide catalysts 11 afforded (3R)-glutarate 6 in more than 90% yields with up to 90% ee. Treatment of 6 with methyl cyanoacetate in the presence of diethyl pyrocarbonate (DEPC) furnished C7N1 building block 5 via C5+C2N1 cyanide-free strategy in 86% yield under McClure’s reaction condition. The next steps were Krapcho reaction, deprotection, Narasaka reaction, protection, hydrogenation, Paal-Knorr reaction, deprotection and salification. The most advantage was eco-friendly cyanide-free installation of cyano type side-chain.In chapter 3, a novel approach toward rosuvastatin calcium (3-1) has been accomplished based on Keck asymmetric allylation of substituted aldehyde (10). (3S)-homoallylic alcohol 9 has been prepared from 10 in Keck allylation condition in up to 80% yields with up to 95% ee. VO(acac)2-catalyzed asymmetric epoxidation of 9 yield (2R,4S)-epoxy 8, then NaCN-openning and Pinner reaction to afford (3R,5S)-ester 6. The most advantage was adopting novel strategies to construct chiral centers of 6 which avoided Narasaka reaction condition. The next steps were protection, hydrogenation, oxidation, Wittig reaction, deprotection and salification. In addition, the absolute configuration of(3R,5S)-5 was unambiguously confirmed by NOESY spectra.In chapter 4, the advances in synthesis of the key ABCD cycles building block for eburnamine-vincamine alkaloids was reviewed.The aim of our studies is to develop new asymmetric synthesis of Katsube nitrile (5-5) by utilizing Pictet-Spengler cyclization as a key reaction.In chapter 5, a novel and efficient synthesis of 5-5 was achieved via a diastereoselective Pictet-Spengler cyclization and TBD-catalyzed condensation to assemble amide as the key steps in 20%(cis-5-5) and 5%(trans-5-5). The primary results of this research provided a possibility for the synthesis of eburnamine-vincamine alkaloids. In addition, the absolute configuration of 6 were confirmed by X-ray single crystal diffraction.