The Study Of Synthetic Process Of Cholanolide

Cholanolide which was discovered by Prof.Weishan Zhou is a analogue of plant hormone Brassinolide is characterized by structure simple,easy to synthesis,highly biologically active,and promoting crop production.The purpose of this thesis is to design a new synthetic route of cholanolide,to optimize the synthetic process and to facilitate industrial production,to widespread use cholanolide in crop production.The synthesis of cholanolide in this paper by means of using cheap and ready availability hyodeoxycholic acid as raw materials,selective reduction of NaBH₄ as key step,methyl 3a-hydroxy-6-ketone-5a-H-cholanoate ester as the key intermediate,was achieved by esterification,oxidation,selective reduction,transposition,lactonization,in five steps.In the synthetic study,hyodeoxycholic acid dissolved in methanol with catalytic amount of concentrated sulfuric acid generate methyl hyodeoxycholanoate ester followed by working out with benzene generate methyl hyodeoxycholanoate ester-benzene complex in the yield of 98%;Oxidation of the methyl hyodeoxycholic acid ester-benzene complex by Jones reagents give methyl 3,6-diketone-5β-H-cholanoate ester in the yield of 96%;Selective reduction of methyl 3,6-diketone-5β-H-cholanoate ester by NaBH₄ in methanol gets methyl 3-hydroxy-6-ketone-5β-H-cholanoate ester in the yield of 80%;Transposition of methyl 3a-hydroxy-6-ketone-5β-H-cholanoate ester in methanol with 2.5%HC1,provides the key intermediate methyl 3a-hydroxy-6-ketone-5a-H-cholano ate ester in the yield of 92%;Lactonization of the key intermediate—methyl 3a-hydroxy-6-ketone-5a-H-cholanoate ester by Baeyer-Villiger reaction obtains targte molecules-cholanolide in the yield of 90%;and by the total yield of 60%in five steps.On completion of this new synthetic route of cholanolide,our interests transfered to study the new synthetic process.Esterization of hyodeoxycholic acid dissolved in methanol with the catalytic amount of concentrated sulfuric acid generates followed by working out with benzene to generate methyl hyodeoxycholanoate ester-benzene complex in the yield of 98%;Green oxidation of methyl hyodeoxycholanoate ester-benzene complex with catalytic amount PDC-H5IO6-KOAC generate methyl 3,6-diketone-5β-H-cholanoate ester in the yield of 85%;Selective reduction of methyl 3,6-diketone-5β-H-cholanoate ester with NaBH₄ in methanol followed with 2.5%HC1 by two steps one pot gives the key intermediate methyl 3-a-hydroxy-6-ketone-5a-H-cholanoate ester in the yield of 90.1%;Lactonization of the key intermediates methyl 3a-hydroxy-6-ketone-5a-H-cholanoate ester provides the target molecule 3a-hydroxy-7-oxa-6-ketone-B-homo-5a-H-cholanoate ester-cholanolide in the yield of a 94.4%with total yield of 70.8%in four steps.In the study of synthetic process of cholanolide,a green oxidation reaction was appliction for the synthesis of the target molecule,and the amount of chromium trioxide was significantly reduced to protect from the pollution of the environment,and to achieve the goal of green environmental protection.The selective reduction and transposition performed in two steps one pot,shortening the reaction steps from five to four,reducing the unit operation and further promote the total yield.The lactonization reaction conditions was optimized and reduced the amount of trifluoroacetic acid anhydride,reducing the cost of production.All intermediates for every step in the synthetic route was crystals to facilitate purification by recrystallization.By Optimization of synthetic process of Cholanolide,the synthetic route is characteristic by short,high total yield,reaction conditions of every steps as mild,environment friendly,the unit reaction as easy to operation,intermediate of each step as easy purification,scalable,that is to say,low cost,safety,environment friendly,easy to industrialization.It is laid foundation that application of the Cholanolide to agricultural production is available...