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Rules which correlate structure and insecticidal activity of pyrethroids have evolved over the last thirty years from the results obtained in the testing of various synthetic pyrethroids. The major portion of these rules have dealt either with the development of new alcohol moieties or variations in the unsaturated side chain of the cyclopropane ring. There has been very little work done concerning modifications of the cyclopropane ring. This study was initiated to discover the affect of substituting an aziridin ring for the cyclopropane ring found in pyrethroids.

This report discusses research concerning synthetic applications of enaminoketones. The work may be divided into four parts as follows: a) replacement of the dimethylamino group of certain enaminones by other amine groups through a simple procedure; b) formation of 3-alkyl-pyrazoles; c) formation of 2-amino-4-alkyl-pyrimidines; d) synthesis and subsequent reduction of iminium salts. The starting materials (E-1-(N,N-dimethylamino)-1-alkene-3-ones) have been condensed with hydrazine and guanidine to form pyrazoles and pyrimidines, respectively. The same starting materials have been reacted with POCl3 in CH2Cl2 to produce chlorovinyliminium salts. These have then been reacted in situ with reducing agents to produce chlorovinyl amines. Additionally, the experimental procedures used to produce these products are revealed, and the physical properties of the products are given. Recommendations for future research are made.

The biosynthesis of virginiamycin S₁, a macrocyclic peptidolactone antibiotic, was studied by growing a strain of Streptomyces virginiae in a complex medium and observing the incorporation of radiolabeled compounds into the antibiotic. These studies have established several of the biosynthetic precursors of virginiamycin S₁. L-(U-14C)-Proline and L-(U-14C)-threonine were effectively incorporated into the respective amino acid components in the antibiotic. N-Methyl-L-phenylalanine was shown to arise from L-(U-14C)-phenylalanine and L-(methyl-14C)-methionine. L-(U-14C)-Phenylalanine was also efficiently incorporated into L-phenylglycine. The origin of the remaining three components was less clear. A small amount of L-(U-14C)-threonine was observed in D-α-aminobutyric acid. A biosynthetic pathway is known between these two amino acids which suggests that L-threonine may be the biosynthetic precursor of D-α-aminobutyric acid. Both L-(U-14C)-aspartic acid and L-(U-14C)-lysine were incorporated into 4-oxo-L-pipecolic acid and 3-hydroxypicolinic acid. A biosynthetic pathway was hypothesized to explain these results. / Master of Science

A comparative synthetic study of a series of six 1,2,3,4,5-pentaphenyl-2,4-cyclopentadiene alkyl ethers was investigated. It was determined that the most efficient route to these ethers was not the most generally accepted route to ethers - the Williamson Reaction - but rather a solvolysis reaction between 1-bromo-1,2,3,4,5-pentaphenyl-2,4-cyclopentadiene and the appropriate alcohol. Thermal rearrangement of the ethers had been expected to rearrange by a [1,5]-sigmatropic shift of the phenyl group in the 1-position to yield the corresponding enol ether. However, this appeared to occur only as a trace in some cases. Rather, the major product of the thermal rearrangements of these ethers was actually the elimination product, the hydrocarbon, 1,2,3,4,5-pentaphenyl-2,4-cyclopentadiene. The elimination is most likely the result of a retro-ene reaction. / Ph. D. / incomplete_metadata

A formal total synthesis of aphidicolin, an important antitumor agent, has been accomplished. Completion of this synthesis required the development of novel methodology. Virtually all of the previous syntheses of aphidicolin share a common difficulty in the construction of the C-9 and C-10 vicinal quaternary centers. In order to solve this problem an investigation into the Michael reaction was launched. This study has revealed that steric encumbrance may be overcome by electronic activation of the acceptor. In fact, two withdrawing substituents were found to make possible the addition of the kinetic enolates of cyclohexenones to β, β-disubstituted acceptors. Several combinations of carboethoxy, cyano, and sulfinyl substituents were utilized. Also, use of sulfinyl butenolides as acceptors demonstrated that considerable stereochemical control may be exercised over the Michael reaction. In addition to work on the Michael reaction, the utility of a novel annulation procedure was demonstrated in the one-pot construction of the AB rings of aphidicolin. The required desulfurization of an α-sulfinyl lactone in the presence of an enone resulted in the development of a new, mild desulfurization agent. Some difficulty was encountered in the dissolving metal reduction of the A ring enone to provide the required trans decalin stereochemistry of the AB ring system of aphidicolin. However, this problem was solved by the construction of the D ring of aphidicolin prior to the dissolving metal reduction. This work resulted in the synthesis of an intermediate in Corey's total synthesis of aphidicolin. This synthesis is approximately 15 steps long, which is competitive with the shortest reported synthesis of aphidicolin. Furthermore, this synthesis is the most efficient reported to date, providing the natural product in approximately 10% overall yield. / Ph. D.

Three 2, 5-dialkyl-1, 3, 4-triphenyl-2, 4-cyclopentadien-1-ols and 2, 5-di(t-butyl)-1, 3-diphenyl-2, 4-cyclopentadien-1-ol were prepared from their precursor ketones using phenyllithium and Grignard reagent. In general, the phenyllithium reagent produced products faster and in better yield and purity than the Grignard reagent. The alcohols were rearranged thermally to obtain the appropriate ketones and to obtain information about the relative rates of the rearrangement. The rearrangement of the three 2, 5-dialkyl-1, 3, 4-triphenyl-2, 4-cyclopentadien-1-ols were studied kinetically and the results compared with those obtained from similar studies on 1,2,3,4,5-pentaphenyl-2,4-cyclopentadien-1-ol. The alcohols all possessed energies of activation and enthalpies of activation which were essentially identical, these supporting earlier theory that no linear free energy relationship (LFER) exists in these rearrangements and that a purely concerted mechanism exists in these cases. The rate of reaction for 15,16,17—triphenylbicyclo[12.2.1] heptadeca-14,16-dien-1-ol was very much faster than any other studied alcohol. The difference in this rate is thought to be due to the severe steric restraints that are present in this alcohol. The entropy of activation for this strained alcohol was shown. to be much less than for the other alcohols. / Ph. D.

A series of eight l-substituted-2,3,4,5-tetraphenyl-2,4-cyclopentadien-l-ols were efficiently synthesized by the addition of the appropriate organometallic reagent to tetracyclone. It was determined that the steric and electronic nature of the migrating groups played a predictable role in the [l,5]-sigmatropic rearrangement of these compounds. Electron donating groups increased the rate of migration whereas electron withdrawing substituents were responsible for slowing the migration. Likewise, smaller groups accelerated the rate while bulky groups deterred the migration. Consequently, the experimental evidence supports the originally proposed charge separated transition state. The Michael addition of potassium cyanide to tetracyclone afforded upon protonation a diastereomeric mixture of the cis (kinetic product) and the trans (thermodynamic product) 4-cyano-2,3,4,5-tetraphenyl-2-cyclopenten-l-ones. Finally an efficient synthesis of 2,3,4,5-tetraphenyl-2(1H)-pyridinone (90%) resulted from the acid promoted addition of sodium azide to tetracyclone. The presence of an intermediate bicyclic triazoline eliminated the Schmitt mechanism as a viable reaction pathway. / Ph. D.

The 2-aryl-2,3-dihydroquinolin-4(1H)-ones were prepared via acid-catalyzed cyclization of the corresponding 2-aminochalcones, which were in turn, prepared by base-promoted Claisen-Schmidt aldol condensation of 2-aminoacetophenone and benzaldehyde derivatives. The 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones were prepared by reacting 2-aryl-2,3-dihydroquinolin-4(1H)-ones with N-bromosuccinimide (NBS) in carbon tetrachloride-chloroform mixture at room temperature. The 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones were subjected to palladium-catalyzed Suzuki-Miyaura cross-coupling reaction with arylboronic acid using dichlorobis(triphenylphosphine)palladium(II)-tricycohexylphosphine as catalyst mixture and potassium carbonate as a base in dioxane-water under reflux to afford the corresponding novel 2,6,8-triaryl-2,3-dihydroquinolin-4(1H)-ones in a single-pot operation. The latter were subjected to thallium(III) p-tolylsulfonate in dimethoxyethane under reflux to yield the 2,6,8-triarylquinolin-4(1H)-ones. The 2,6,8-triaryl-2,3-dihydroquinolin-4(1H)-ones were treated with molecular iodine in refluxing methanol to afford the corresponding 2,6,8-triaryl-4-methoxyquinolines. All the new compounds were characterized using a combination of 1H NMR & 13C NMR spectroscopy, IR and mass spectroscopic techniques. / Chemistry / M.Sc. (Chemistry)