Synthesis And Agricultural Antifungal Activity Of Atural Products Of Nortriterpenoids Walsucochin B,walsucochinoids M/N And Their Key Intermediate Derivatives

Natural products are important resources for the creation of new pesticides and play a pivotal role in the pharmaceutical and agrochemical industries.The natural products walsucochin nortriterpenoids containing 6/6/5/6 ring system are novel in structure and have broad biological activities such as antifungal,antitumor and anti-inflammatory,so they have received widespread attention.However,due to the extremely low content of such compounds in nature,and the complex fused-ring molecular skeleton structure that makes it highly challenging to synthesize efficiently,this current situation limits people’s in-depth research on their agricultural activities.In this paper,using commercially available trans,trans-farnesyl bromide as starting material,the natural products walsucochin B,walsucochinoids M/N were designed and synthesized,and the key intermediates were derivatized and their preliminary agricultural antifungal activities were investigated.The specific contents are as follows:In the first part,walsucochin nortriterpenoids with important biological activity were taken as our research object.Commercially available trans,trans-farnesyl bromide were used as starting material to obtain epoxy cyanide compounds through alkylation and hydroxyl bromination reaction.Then the free radical tandem cyclization reaction initiated by the titanium reagent was employed to construct the basic skeleton of the nortriterpenoids containing the 6/6/5/6 ring system in one step.Through the Cu-mediated remote C-H hydroxylation reaction,the oxygen atom was selectively introduced at the 7 position of the B ring.The aromatic D ring was then constructed in one step by using the Michael addition reaction and the Aldol reaction.Finally,the total synthesis of walsucochin B,walsucochinoids M and N were achieved through some structure modification in 12-13steps.The synthesized compounds were characterized by hydrogen nuclear magnetic resonance spectroscopy（¹H-NMR）,carbon nuclear magnetic resonance spectroscopy(¹³C-NMR),and electrospray mass spectrometry（ESI-MS）.This work provides an efficient synthetic strategy for the preparation of natural products of the nortriterpenoids containing 6/6/5/6 ring system.In the second part,the key intermediates 2-3 and 2-5 for the synthesis of walsucochin B and walsucochinoids M/N were taken as starting materials,and a series of analogs were synthesized through deprotection,acetylation and IBX oxidation,respectively.Using the mycelial growth rate method,the target compounds were tested against some agriculturally important plant pathogens,such as the rape sclerotinia sclerotiorum（Sclerotinia sclerotiorum）,apple rot pathogen（Valsa mali）,wheat head blight（Fusa Hum graminearum sehw）,and grape gray mold（Botrytis cinerea）.The results show that some compounds have good antifungal activity against the tested fungi:Compounds 3-14,3-15 and 3-16 have relatively significant antifungal activity.Among them,the EC₅₀ values of 3-14 for Sclerotinia sclerotiorum,Valsa mali and Botrytis cinerea were 17.35μg/m L,19.08μg/m L and 11.72μg/m L,respectively;the EC₅₀ values of 3-15 for Sclerotinia sclerotiorum,Valsa mali and Botrytis cinerea were 8.14μg/m L,19.16μg/m L and 14.17μg/m L,respectively;the EC₅₀ values of 3-16 for Sclerotinia sclerotiorum,Valsa mali and Botrytis cinerea were22.18μg/m L,29.55μg/m L and 24.87μg/m L,respectively.Compounds 3-14,3-15 and3-16 are expected to be promising lead compounds for further structural optimization.At the same time,it laid the foundation for the research of developing new fungicides based on the natural products walsucochin nortriterpenoids containing the 6/6/5/6 ring system.