Dissertations and Theses @ UNI
Availability
Open Access Thesis
Keywords
Verruculotoxin;
Abstract
The compound verruculotoxin, a natural mycotoxin, was isolated in 1974 and found to be biologically active, having anesthetic properties. Two theories have been proposed to explain the biological activity of verruculotoxin. The first theory states that verruculotoxin is not the biologically active compound, but, rather, as a result of metabolism in the body, a biologically active metabolite is produced. The second theory states that the biological activity of verruculotoxin is dependent upon the molecules ability to mimick various co-formations with respect to the spatial arrangement of the aromatic ring and nitrogen atom. These theories are used to explain the activity or lack of activity of a series of previously synthesized structural analogues of verruculotoxin. In an effort to continue the study on the structure activity relationship of verruculotoxin, the compound (3S,8aS) 3-(2-phenyl-2-propyl-)-l-oxo-octahydro-2H-pyrido[l,2a]pyrazine was synthesized as a model compound to test the proposed theories for biological activity. Synthesis was accomplished in five steps starting from 2-amino-3-phenyl-3-methylbutanoic acid, which was prepared by the method of Jonsson and Mikiver (Acta Pharm. Suec. 1976, 13, 75-78). In the first step of the synthesis, the amino acid was reduced to 2-amino-3-methyl-3-phenylbutanol by means of a mild single-step reducing agent. This single-step reduction was done according to the method described by Saund et al. (Int. J. Peptide Protein Res. 1973, ~, 7-10). The second step involved coupling the amino alcohol with picolinic acid. This resulted in the formation of N-(lhydroxy-3-methyl-3-phenyl-2-butyl-) picolinamide. The coupling was carried out according to the method described by Vaughn and Eichlor (J. Am. Chem. Soc. 1953, 75, 5556-5560) and involved the aminolysis of a mixed anhydride. The resulting amide alcohol was converted to N-(lchloro-3-methyl-3-phenyl-2-butyl-) picolinamide using thionyl chloride. Cyclization of the amide chloride in DMF led to 3-(2-phenyl-2-propyl-)-l-oxo-3,4-dihydro-2H-pyrido[l,2a] pyrazinium chloride, which was then hydrogenated to yield the final product, 3-(2-phenyl-2-propyl-)-l-oxo-octahydro2H-pyrido[l,2a]pyrazine. Infrared and 360 MHz proton and carbon NMR allowed the identification of the structures of the intermediates and final compound.
Year of Submission
1987
Degree Name
Master of Arts
Department
Department of Chemistry
First Advisor
James G. MacMillan
Second Advisor
Paul E. Rider
Third Advisor
LeRoy McGrew
Date Original
1987
Object Description
1 PDF file (133 leaves)
Copyright
©1987 Karen Earlene Couch
Language
en
File Format
application/pdf
Recommended Citation
Couch, Karen Earlene, "The Synthesis of (3s, 8aS) 3-(2-Phenyl-2-Propyl-)-1-Oxo-Octahydro-2H-Pyrido[1, 2a] Pyrazine as a Model Compound to Test Proposed Structure-Activity Relationships and Metabolism of the Natural Mycotoxin and Muscle Relaxant: Verruculotoxin" (1987). Dissertations and Theses @ UNI. 2403.
https://scholarworks.uni.edu/etd/2403
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