The Total Synthesis of (-)-Prezizaene, (-)-Prezizanol, and Other Perzizanoid Sesquiterpenes
Roach, Paula Marianne
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https://hdl.handle.net/2142/67281
Description
Title
The Total Synthesis of (-)-Prezizaene, (-)-Prezizanol, and Other Perzizanoid Sesquiterpenes
Author(s)
Roach, Paula Marianne
Issue Date
1981
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
Language
eng
Abstract
The synthesis of four related sesquiterpenes was accomplished by elaboration of the chiral precursor pulegone. The ring system of (-)-prezizaene and (-)-prezizonal was constructed by intramolecular ring expansion of a diazo ethyl hydrindanone. (-)-Georgeone and (-)-georgeol containing a C-6 methyl group were formed by pinacolic rearrangement of a 3a,6-ethanoindene-diol. Favorskii rearrangement of (+)-pulegone and ozonolysis furnished ethyl 5-methyl-2-oxo-cyclopentane carboxylate which was annelated with methyl vinyl ketone to give a mixture of diastereomeric hydrindenones. Hydrogenation to ethyl 3-methyl-6-oxo-cis-hexahydroindane-3a-carboxylate was stereospecific. Ketone protection, reduction of the ester and sulphonylation gave 7a-hydroxymethyl-1-methyl-cis-hexahydroindane-5-one ethylene ketal as a single isomer after crystallization. An X-ray structure determination confirmed the all cis stereochemistry at the three chiral centers. Reduction and hydrolysis afforded a dimethyl ketone which was identical with a sample prepared independently.
Cyanide displacement under solid-liquid phase transfer conditions and reduction of the resulting nitrile provided a ketal amine. Benzoylation, hydrolysis, and nitrosation gave an N-nitroso amide. Treatment with potassium t-butoxide in t-amyl alcohol formed the diazo group which, after intramolecular addition to the ketone and rearrangement, afforded a ca. 1:1 mixture of two tricyclic ketones. These were identified as a 3-methyl-2,3,5,6,8,8a-hexahydro-1H-3a,6-methanoazulene-7(4H)-one and 3-methyl-octahydro-6H-3a,7-methanoazulene-6-one by selenation of the latter and oxidation and elimination to an (alpha),(beta)-unsaturated ketone. Alkylation, methyl lithium addition, and dehydration gave (-)-prezizanol and (-)-prezizaene which were completely identical with the natural products.
Oxidation of the ketal amine followed by hydrolysis afforded a nitro ketone which underwent aldol condensation to a tricyclic nitro alcohol containing the 3a,6-ethanohydrindane skeleton. Ozonolysis of the nitronate salt to 6-hydroxy-3-methyl-octahydro-3a,6-ethano-3aH-inden-5-one and methyl lithium addition provided a mixture of diasteromeric diols which under acidic conditions, underwent pinacolic rearrangement to a single 3a,6-methanoperhydroazulene-7-one. Methylation gave (-)-georgeone (3,6,8,8-tetramethyl-2,3,5,6,8,8a-hexahydro-1H-3a,6-methanoazulene-7(4H)-one, and hydride reduction furnished (-)-georgeol. The spectral properities of both compounds were comparable to those of the natural products.
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