Synthesis Of Moxidectin And SO₂F₂-participated Esterification Of Carboxylic Acids With Alcohols

This thesis contains the following two parts.Part 1:With the development of science technology and medical treatment,parasitic diseases are not fatal,but they threaten the advancement of animal husbandry.As the drug abused,the problem of resistance are become a universal issue.Recently,scientists have reported a new type of macrolide antiparasitic drug,which is a semi-synthetic compound,mainly divided into avermectins and milbemycins.Moxidectin arouse the attention of scientist among the drugs in the milbemycins family,which has high resistance and excellent anti-parasite activity.In view of the importance,the first part of this paper investigates the synthesis of moxidectin,which is divided into the following two aspects:1.The research progress of some promising new antiparasitic drugs on the market was briefly reviewed.2.A novel synthetic route was designed to synthesize moxidectin.Using nemadectin as the raw material,the products of moxidectin were prepared by four steps of up protection,oxidation,oximation and deprotection.At the same time,the conditions of each step are optimized to get the optimal reaction conditions.Part 2:Ester compounds are one of the most basic organic compounds and are widely used as synthetic intermediates,drags and functional materials.Acid catalysis and esterification of carboxylic acid with alcohol mediated by condensation reagent are the two most commonly used methods for synthesis of ester.However,some of these methods still have disadvantages such as corrosiveness,high cost and harsh conditions.Sulfuryl fluoride(SO2F2)gas is a kind of low toxicity,low cost,stable reagent,Sulfuryl fluoride as an excellent insecticide has been widely used in industry and agriculture for decades.Since the click chemistry based on Sulfuryl fluoride was reported by K.B.Sharpless in 2014,Sulfuryl fluoride,as an excellent hydroxy-activating reagent,has been investigated in depth by chemists and has been used in the syntheses of aryl nitriles,heterocyclices,ethylenesulfonyl fluorides,diaryl methanes,arylcarboxylic acids,alkynes,nitriles and amides.Our research group has been carrying out the project of poly(per)fluorosulfonyl fluoride(RfSO2F)applied in organic synthesis for more than ten years.In 2009,RfSO2F-mediated esterification,amidation and anhydrization were reported.On the basis of these preliminary results,we investigated the esterification of carboxylic acid and alcohol induced by SO2F2.In view of the importance of esters in pharmaceutical chemistry,our experimental results will lay a solid theoretical foundation for the application of Sulfuryl fluoride in the industrial production of esters.This part mainly includes the following two aspects:1.The methods of ester formation by dehydration of carboxylic acids and alcohols induced by various reagents and the important role of thionyl fluoride in organic synthesis in recent years were reviewed.2.The process of inducing the dehydration reaction of carboxylic acid and alcohol under alkaline conditions to form ester was studied.