Furanmethylcation-induced Three-component Thioesterification And Synthesis Of Natural Product (-)-newbouldine Based On Intramolecular NN Coupling

Furfural can be extracted from inedible lignocellulose such as corn stalks and cotton husks.It is an important renewable biomass resource.It can be used not only as a chemical raw material for fine chemicals,but also for biofuels.The future has the potential to replace non-renewable resources such as oil and gas.Furan derivatives are key structural frameworks found in many biologically active molecules,and they are also commonly used as "tools" in synthetic chemistry.The low aromaticity of the furan ring enables it to undergo dearomatization by oxidation reaction,ring-opening rearrangement reaction,cycloaddition reaction,etc.,and further rearrangement cyclization into new carbocyclic or heterocyclic compounds.Therefore,the development of novel dearomatization methodologies for furan is of great significance in organic chemistry.A variety of amino acids in the body contain sulfur elements,and the sulfur-containing proteins formed are found in the human heart,kidney,liver and other organs,and are of great significance to human life activities.Among them,thioesters are common sulfur-containing functional groups in these proteins,and thioesterification reactions have been widely used in chemical modification of proteins.In addition,thioesters are also found in a large number of biologically active natural products and small molecule compounds.Thioesters are active carboxylic acid derivatives with similar acylation properties as acid anhydrides.They are important functional groups in organic synthesis.Therefore,the construction method of thioester has attracted wide attention.In this paper,a novel multi-component tandem reaction based on the ring-opening rearrangement of biomass furan was developed for the synthesis of complex enethioester triazole compounds.This reaction uses 5-halofuranol,thiol,and organic azide as raw materials.The acetyl chloride/hexafluoroisopropanol system is used to initiate the formation of furan methyl carbocations,which are connected in series by[3+2]cycloaddition/furan ring-opening/thioesterification reaction has achieved the synthesis of a series of(Z)-configuration enethioester triazole compounds.This method has high step economy,product structure diversity and stereospecificity.The reaction conditions are mild,no metal is involved,and it is not sensitive to air.Simple operation and easy post-processing.Newbouldine is a natural product containing diazo structure extracted from plants of the family Bignoniaceae,which has potential biochemistry for treating dysentery,helminthiasis and migraine.The construction of the diazonium structure(N-N bond)is the difficulty and key to synthesize the natural product.The method of FeCl3 catalyzed intra-molecular N-N bond coupling reaction developed by this research group is taken as a key step.We started from L-proline and achieved six-step chemical conversion to achieve a highly efficient and simple synthesis of(-)-newbouldine.This synthetic route is more environmentally friendly and economical,which lays the foundation for large-scale preparation of(-)-newbouldine.