The Synthesis Of Vinylcyclopropane-based Pyrazolone And Pyrazole-fused Pyranone Oxime Alkaloids

Pyrazole alkaloids and pyrazolone alkaloids are a unique five-membered lactam natural product with two consecutive nitrogen atoms,and these skeleton compounds can also be used as leading compounds of many important pharmacologically active molecules.It has antipyretic,analgesic,neuroprotective,antibacterial,anti-tumor and insecticidal activities,and can inhibit acetyl-Co A carboxylase and 4-phosphodiesterase,so it is considered to be a very important pharmacophore group with nitrogencontaining heterocycles.However,due to the potential side effects and low bioavailability of these compounds,the application of these natural products in the field of innovative drug development has been greatly limited.Therefore,it is of great significance to adopt efficient means of organic chemical synthesis to construct new pyrazole alkaloids and pyrazole alkaloids or to introduce specific active skeletons into them to achieve the purpose of enhancing efficacy and reducing toxicity.On the other hand,vinylcyclopropane(VCP)is an indispensable multi-functional skeleton in natural products and medical drugs,which is widely distributed in a variety of bioactive molecules.Because of its unique pharmacological action,it has aroused the interest of researchers in various research areas.Therefore,we believe that the development of an innovative chemical synthesis route,which effectively combination of these two active groups with important biological activities,may construct a unique pharmaceutical chemical skeleton.This highly functional structural skeleton can also be used as an important lead compound in organic synthesis and can be further constructed into a pyrazolopyran framework with effective biological activity and pharmacological activity.To realize the direct conversion between active pyrazole skeleton molecules.This method provides an effective new idea and method for the synthesis and discovery of innovative pyrazolone alkaloids and the mutual transformation of pyrazole alkaloids with different bioactive groups.Focusing on this content,this paper has carried out the following two parts of research on the preparation of VCP-based pyrazolone and pyrazole-fused pyranone Oxime alkaloids:Part 1: Construction of compounds containing VCP-based pyrazolone.Using differently substituted α-arylmethylene pyrazolone 1 and brominated nitroolefin 2 with multiple active sites as starting materials for the proposed [2 + 1] annulation.Successfully constructed highly functionalized VCP-based pyrazolone compounds 3under suitable conditions.A total of 21 new [2 + 1] annulation compounds with different substitutions have been obtained.And the [2 + 1] annulation reaction has good substrate compatibility,which laid a rich substrate foundation for the second part of the construction of pyrazole-fused pyranone OximePart 2: The construction of pyrazole-fused pyranone Oxime.Based on the first part,we investigated the structure of more complex pyrazole derivatives through a sequential process to verify the synthesis potential of [2 + 1] annulation products.Nine representative annulation compounds 3 with different substituents were selected as substrates for the second step reaction.After simple experiments,the new rearrangement products 6 with pyrazole-fused pyranone Oxime skeleton were obtained,and the yield of the product was medium.