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https://hdl.handle.net/2142/70238
Description
Title
Synthesis of the Ophiobolin Ring System
Author(s)
Muskopf, Jack Warren
Issue Date
1984
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Abstract
The synthesis of 1-oxo-1H-dicyclopenta(a,d)-5-carboxylates developed in these laboratories by Senter, Baker, and Coates has been extended to a synthesis of a 5-8-5 ring system having the relative configuration of the ophiobolin and ceroplastol sesterterpenes. The relative stereochemistry of three of the four asymmetric centers was determined by x-ray crystallographic analysis of an intermediate iodide. Incorporation of a (DELTA)('7,8) double bond, which is a structural feature common to most ophiobolins and ceroplastols, was effected by dehydroiodination of an intermediate iodo ketone that was prepared in one step from the corresponding dicyclopentacyclooctene carboxylic acid. A 5-8-5 ring system with the relative configuration of the fusicoccin family of diterpenes at C-6, C-7, and C-11 was also synthesized by the same annelative two-carbon ring expansion of an unsubstituted trans-hydrindanone. Analysis of the chemistry of these 5-8-5 ring systems was simplified since most chemical transformations were carried out on single diastereomers of known relative stereochemistry.
Two approaches were examined for the synthesis of a trans-hydrindanone suitably functionalized for use as starting material in the total synthesis of ophiobolin or ceroplastol natural products. Heterogeneous catalytic hydrogenation of tricyclic (DELTA)('3a,4)-perhydroindenone lactones substituted at C-3 afforded predominantly the undesired cis-fused products. Lithium in ammonia reduction of the corresponding enone hydroxy acid also gave the cis ring fusion.
Pyrrolidine induced cyclization of methyl 2,4-dimethyl-2-(3-oxobutyl)-1,3-dioxocyclohexane-4-acetate furnished a napthalenone with the methyl acetate substituent at C-5. The desired C-7 substituted napthalenone was not detected. The reaction of the same trione with either sodium methoxide in anhydrous methanol or diazabicyclo(5.4.0)undec-5-ene in tetrahydrofuran furnished an enone acid and a (delta)-lactone. A novel mechanism is proposed which rationalizes the formation of these products. Isolation of similar products from other substituted cyclohexandiones under strictly anhydrous conditions provided additional evidence that these products arise from rearrangement of kinetically formed bridged ketols via twistane intermediates.
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