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Stereoselectivity Of Nitroso-ene Reaction And Its Application In Alkaloid Synthesis

Posted on:2021-05-28Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:2381330614456330Subject:Pharmaceutical Engineering
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This thesis focuses on the chemical reactivity of the nitroso-ene reaction,designs and develops new synthetic methods,and applies them to the synthesis of natural products.Nitrogen-containing heterocycles and natural products play an important role in medicine development.The development of efficient synthetic methods is of significance for the discovery of new lead compounds.In this thesis,the natural products bromopyrrole alkaloids Manzacidins,Clathramides and nitrogen-containing heterocyclic 1,3-benzodiazepine derivatives are selected as research objectsto explore the application of different types of nitroso-ene reactions in natural products with nitrogen-containing quaternary carbon center structures and to expand nitroso-ene substrates.The first part of this thesis is to investigate the stereoselectivity of the nitroso-ene cyclization reaction.We used a highly diastereoselective nitroso-ene cyclization reaction to obtain ?-lactams with quaternary carbon centers.The selected examples presented herein reveal that the intramolecular hydrogen bond would provide conformational restraint to facilitate excellent facial selectivity in the nitroso-ene reaction via a chair-like transition state.The sterically bulky amino group also provides excellent stereochemical control possibly through steric repulsion.Therefore,through this simple method,the key Ohfune intermediates were constructed,and the form synthesis of Manzacidin A and C was completed.The second part of this thesis is the studies towards clathramides.Starting from the key intermediate of ?-lactam,a synthetic strategy based on the NE reaction was devised for the alkaloid clathramides.The challenge in this synthetic work is to construct a five-membered ring of imidazole.Further research is ongoing.The third part of this dissertation is to study the synthetic method of constructing 1,3-benzodiazepine derivativesvia the 7-endo type nitroso-ene reaction.After converting the commercially available orthoaminoacetophenone series compounds to hydroxamic acid,a 7-endo type nitroso-ene reaction occurred in the CuCl2/H2O2 system to produce 1,3-benzodiazepine derivatives.
Keywords/Search Tags:Nitroso-ene reaction, bromopyrrole alkaloid, Manzacidins, Clathramides, intramolecular hydrogen bond, 1,3-benzodiazepine
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