Discovery of Parts Per Million level organocatalytic asymmetric annulations Synthesis of Chiral Drug Like molecules

Abstract

Discovery of Parts-per-Million Level, Organocatalytic Asymmetric newlineAnnulations: Synthesis of Chiral Drug-Like Molecules newline1. Abstract: newlineThe first chapter illustrates a synthetic methodology for the preparation of chiral newlinemethanobenzo[7]annulenes. In this protocol, 3-alkyllawsones are selectively reacted with and#945;- newlinealkyl nitroethylenes under 500 parts-per-million (ppm) quinine-NH-thiourea-catalysis to newlinefurnish the chiral methanobenzo[7]annulenes in up to gt99% ee with gt20:1 dr and up to 1820 newlineTONs through tandem Michael/Henry [3+2]-annulations. These asymmetric ppm-level, newlinecatalytic tandem [3+2]-annulations would be highly inspirational to design many more ppmlevel newlineorganocatalytic reactions, and at the same time these final molecules are basic skeletons newlineof antibiotics. newlineIn the second chapter, we have described the synthesis of bicyclo[3.2.1]octanes in very good newlineyields with excellent enantio and diastereoselectivities through organocatalytic [3+2]- newlineannulations from hydroxy-p-quinone and nitroethylene. The bicyclo[3.2.1]octane unit is newlinepresent in both natural and synthetic compounds that possess various biological activities. This newlinebicyclo[3.2.1]octane core moiety acts as a reactive intermediate in various stereoselective newlinesynthetic transformations. These systems form a fundamental building block for biologically newlinesignificant active molecules such as sesquiterpenoids, lignans, and alkaloids. newlineIn the third chapter, we have developed an unprecedented protocol for the synthesis of newlinevarious natural products such as embelin, rapanone, irisoquins, from three-component newlinereductive alkylation method, which we have been working on over the past two decades. These newlinenatural products exhibit various pharmacological and wide range of biological activities newlineincluding antihelmintic, analgesic, antitumor and antioxidant properties. newline2. Introduction newlineIn the early era of organocatalysis, it was very predominant to find catalytic loadings of up newlineto 20-30 mol%, which is quite disappointing for many chemists who are accustomed to use newlinemetals or enzymes