Studies On The Synthesis Of Chrom-nes And Natural Marine Product Puupehenone

Chromenes are a class of important organic oxygen-containing heterocyclic compounds,which are the key intermediates of many drugs and natural products.Previous investigation shows that 4H-chromenes possess various biological activities,such as antioxidant,antibacterial,antifungal,antiviral,antitumor.In this thesis,a new method for the preparation of 4H-chromenes was developed by using simple phenol and ketone compounds as raw materials.Puupehenone is a marine natural product isolated from deep-sea sponge,which contains the structure of chromene and has potential application value in the field of medicine because of its antitumor,antituberculosis,antibacterial,antioxidant and other pharmacological activities.Based on the research progress and organic chemistry mechanism,a total synthesis method of puupehenone was designed.This thesis mainly includes the following two contents:1.Total synthesis of marine natural product puupehenone.This section carried out the total synthesis research on natural products puupehenone and related derivative.A retrosynthetic analysis of puupehenone was comleted according to the structural characteristics,which disassembled its chromene ring into aromatic skeleton and terpene-ring segments.Then,the synthetic strategy of two separate segments was designed.The next was the coupling of the two segments and finally the marine natural products puupehenone and puupehenol was synthesized through the structural modification.In addition,the synthesis of dimer derivatives bispuupehenone was also explored and multiple synthetic routes were designed.Taking sclareolide as raw material to synthesis the terpene-ring segments,12 intermediates were synthesized by methylation,oxidation,reduction,opening ring etc.The aromatic skeleton was prepared from vanilline by the reaction of phenol coupling,aldehyde oxidation,decomposition,methylation,etc and 16 intermediates were obtained.In the end,the synthesis attempt onconstruction of key skeleton were carried out by the methods of the palladium catalyzed carbene migration reaction,Friedel-Crafts alkylation and the monomer binary series reaction.2.Synthesis of 4H-chromenes.In this part,4H-chromenes afforded from the simple phenol and ketone compounds through the tandem reaction and dehydration step by the safe and inexpensive iron catalyst.After optimizing of the reaction conditions,25 representative 4H-chromenes were synthesized to verify the universality of the method.Finally,two intermediates were isolatedwhich were used to study the mechanism of the reaction and a possible mechanism of the reaction was proposed.Compared with other reports,this synthetic method contains the advantages of simple operation,inexpensive catalyst and high reaction efficiency.In this thesis,a new method for synthesis of 4H-chromenes which possess the advantages of simplify operation,inexpensive,and wide applicability,etc,was developed.The total synthesis of puupehenone and puupehenol was completed.The synthesis study of dimer derivative bispuupehenone was carried out and a series of the key intermediates were synthesized.