A Concise Synthetic Study Of The Natural Products Verbalactone And (+)-(3R,5R)-3-hydroxy-5-decanolide And The Key Intermediates Of Orlistat

The Natural products Verbalactone,(+)-(3R,5R)-3-hydroxy-5-decanolideand orlistat are all ring ester which is contain the chiral hydroxy,and they all have the a huge biomedical value.In this paper,we choose the asymmetric synthesis of Verbalactone,(+)-(3R,5R)-3-hydroxy-5-decanolide and orlistat as our research objective,and design two similar synthetic routes to achieve the asymmetric synthesis of this three compounds.The following text is divided into four chapters.In the first chapter,we summarizes the background and significance of this research project,including the sources of natural product,the development of natural productand,the significance of natural productand in the of New Drug Research,the pharmaceutical intermediates,the development and significance of chiral drugs,the bacterial resistance to antibiotics and antimicrobial drugs,and the asymmetric research progress of natural product Verbalactone,(+)-(3R,5R)-3-hydroxy-5-decanolide and orlistat.In the Second chapter,our studies introduces the method used in the construction of the three target molecules' chiral center and the designed synthetic strategy,and we also make analysis around this synthetic strategy.This synthetic strategy unify the synthesis of Verbalactone,(+)-(3R,5R)-3-hydroxy-5-decanolideand key orlistat intermediates,using a similar route to achieve this three target synthetic molecules.In the third chapter,we introduces the asymmetric total synthesis of Verbalactone,(+)-(3R,5R)-3-hydroxy-5-decanolideand orlistat intermediates.In the research of two similar synthetic routes,first of all,the two raw material through two steps of asymmetric aldol reaction and nucleophilic substitution reaction,synthesized the chiral hydroxyl-y-carbonyl ketoester;and then through asymmetric reduction,the corresponding cis and trans two chiral centers were respectively constructed,then through one-step synthesis reaction,(+)-(3R,5R)-3-hydroxy-5-decanolide were synthesized;through two-step synthesis reaction,Verbalactone were synthesized;through four-step synthesis reaction,the orlistat intermediates were synthesized.The research results provided valuable experience in the later synthesis of antimicrobial drugs and new lose weight drugs.In the fourth chapter,we introduces the detailed synthetic work of Evans chiral auxiliary,Verbalactone and(+)-(3R,5R)-3-hydroxy-5-decanolide and orlistat intermediate.