Studies Directed Toward A Synthesis Of The Sesquiterpene Zizanoic Acid

Author : Hong Chan Wing
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (144 download)

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Download or read book Part 1. Total Synthesis of (-)-khusimone, (+)-zizanoic Acid and (-)-epizizanoic Acid written by Hong Chan Wing and published by . This book was released on 1979 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first part of this thesis describes a total synthesis of three zizaene sesquiterpenes, (-)-khusimone (I), (-)-epizizanoic acid (II) and (t)-zizanoic acid (III), starting from the coirmer- cially available (-) -J-l 0-camphor sulfonic acid ammonium salt (IV). Fusion of the salt IV with solid potassium hydroxide gave (-) - a -campholenic acid (V) which was converted to the corresponding methyl ester VI with methyl iodide and potassium carbonate in refluxing acetone. Ozonolysis of ester VI followed by reductive work-up using triphenylphosphine afforded keto aldehyde VII. Its cyclization to enone VIII was effected by p-toluenesulfonic acid in refluxing benzene. Irradiation of enone VIII with 1,1-diethoxy- ethene followed by hydrolysis of the photoadduct IX gave rise to a mixture of diketones X and XI in a ratio of 5:8. The latter product was converted to the former one by treatment with pyridin- ium bromide perbromide in acetic acid followed by reduction of the resulting enediones XII with zinc in acetic acid. Selective ketalization of diketone X using 2-ethyl-2-methyl- 1,3-dioxolane and p-toluenesulfonic acid gave rise to ketal XIII which was hydrolyzed to the corresponding acid XIV with alkali. Treatment of the sodium salt derived from acid XIV and sodium hydride with methyl magnesium bromide followed by esterification of the resulting hydroxy acid XV with diazomethane afforded alcohol XVI. On treatment with thionyl chloride in pyridine in benzene, alcohol XVI underwent dehydration to give ester XVII which was subsequently reduced by lithium aluminium hydride to alcohol XVIII. Its conversion to the corresponding chloride XIX was effected by phosphorus oxychloride in pyridine. Hydrolysis of chloride XIX with hydrochloric acid and ring expansion of the product XX with ethyl diazoacetate and boron trifluoride etherate gave rise to keto ester XXI. When heated at reflux with sodium hydroxide in ethanol and water, keto ester XXI underwent concomitant decarbethoxylation and cyclization to give (-)-khusimone (I). On treatment with dimethyl sulfonium methyliue y.Lide, (-)- khusimone (I) was transformed to epoxide XXII. Boron trifluoride catalyzed rearrangement of epoxide XXII afforded aldehyde XXIII which was subsequently oxidized with Jones reagent- to give (-)- epizizanoic acid (II). Alternatively, epimerization of aldehyde XXIII to XXIV 7 followed by Jones oxidation resulted in the formation of (t)-zizanoic acid (III). In the second part of this thesis, the preparation of trione XXV, a potential synthetic precursor of cedrenoi.d sesquiterpenes, is described. (-)-a-Canpholenic acid (V) was first, converted to ketone XXVI by treatment with methyllithium. Photcoxidation of ketone XXVI followed by reductive work-up with trietayl phosphite gave rise to epimeric alcohols XXVII which were subsequently oxidized with active manganese dioxide to give enone XXVII, Addition of 1-nitropropane to enone XXVIII was effected by u r - mg potassium carbonate as a base. The salt derived from tJie oroduct XXIX and one equivalent of sodium methoxide in methanol was subjected to ozonolysis. Reductive work-up using dimethyl sulfide afforded trione XXV. Results obtained from the preliminary studies on the transformation of trione XXV to cedrenoid sesquiterpenes are also discussed.