Heliquinomycin, a member of a rubromycin family of natural products, is a complex natural product consisting of a naphthoquinone and an isocoumarin which are linked through a 5,6-spiroketal functionality. The spiroketal also bears a glycosidic linkage. Previous work in our group has developed a method for generating both the naphthoquinone and isocoumarin portions of this natural product. The focus of this work was to develop a method for joining these two halves of the natural product while also allowing for the formation of the spiroketal. The specific goals accomplished include developing a method for extending the allyl-side chain of a model isocoumarin compound, functionalization of an olefin in preparation for forming the spiroketal structure and coupling of the naphthoquinone with the isocoumarin model via a nitrile-oxide [3+2] dipolar cycloaddition. Completion of the natural product will also require several oxidation state adjustments of the naphthoquinone moiety. To that end we were able to carry out the necessary transformations: opening an isoxazole ring, reduction of a quinone ring to an acetylated hydroquinone and oxidation of a trimethoxybenzene ring to a methoxy quinone in attempting a synthesis of the natural product Y-1005.

Styrene is one of many industrially important monomers. Polymerization of unsaturated monomers such as styrene is a troublesome problem during storage, transportation and processing. The problem is attenuated by addition of polymerization inhibitors such as quinone derivatives. Despite the importance of quinone type inhibitors, their chemistry is poorly understood. The goal of this research is to better understand the reaction mechanism and rates of alpha-phenethyl radicals with quinone type inhibitors. cis Azo-alpha-phenylethane was used as a new simple, unimolecular, low temperature source of alpha-phenethyl radicals. The absolute rate constants of five quinone type inhibitors (N-oxide, BQ, QM, tBQ and DPQI) with alpha-phenethyl radicals generated from cis azo-alpha-phenylethane were measured by the radical clock method using the stable nitroxide SG1 as the clock. We found that the trapping rate decreased in the order N-oxide>BQ>QM>tBQ>DPQI. Also product studies of BQ and QM with phenethyl radicals were done to augment previous results.

In this work several self-assembling materials have been designed, synthesized, characterized and studied. These materials were based on synthetic peptides that were obtained through the solid phase peptide synthesis. First, collagen mimics were prepared through the polymerization of collagen-like peptides. Polymerization was done via native chemical ligation and yielded high molecular weight peptide polymers. The collagen-like structure of this polymers was confirmed by circular dichroism spectroscopy, size exclusion chromatography and transmission electron microscopy. Second, the internal structure of peptide amphiphiles was investigated. It was found that the formation of the hydrogen bonding network inside the nanofibers plays an important role in their self-assembly. In the absence of the hydrogen bonding a peptide amphiphile self-assembles into spherical micelles. Finally, the self-assembly of multidomain peptides was studied. The multidomain peptides were designed to combine several regions with different self-assembling motifs. The core region was made out of beta-sheet forming amino acids with the termini regions being either hydrophilic or electrostatically charged. When two of such peptides were mixed together it was found that their nanostructure, composed of fibers can be regulated and the fiber length can be controlled depending on the peptide molar ratio.

Coronatine (1) (Fig 1) is a novel, non-host specific phytotoxin elaborated in the liquid fermentation broths of several different Pseudomonas syringae pathovers. Infection of tomato plants by P. syringae pv. $tomato,\sp1$ Italian ryegrass by P. syringae pv. $atropurpurea,\sp{2,3}$ soybean by P. syringae pv. $glycinae,\sp{3,4}$ and Prunus spp. by P. syringae pv. $morsprunorum\sp3$ induces yellow chlorotic haloes, stunting, and plant tissue hypertrophy due to the production of coronatine.$\sp{2,4}$ Coronatine presents two distinct biosynthetic problems, one being the origin of coronafacic acid (2) the other the origin of the novel amino acid coronamic acid (3) (Fig 1). The investigations presented in this dissertation were directed towards an understanding of the biosynthetic pathway to coronamic acid. Our results from the administration of specifically labeled precursors to Pseudomonas syringae pv. glycinae (PDCC # 4182) suggest that: (1) the retention of the tritium label from (3-$\sp3$H) -L-alloisoleucine rules out the intermediacy of 3-methylene-norvaline on the biosynthetic pathway to coronamic acid, (2) the incorporation of approximately half of the $\sp{15}$N label from a mixture of (2-$\sp{13}$C, $\sp{15}$N)-DL-isoleucine and (2-$\sp{13}$C, $\sp{15}$N)-DL-alloisoleucine indicates that the cyclisation reaction leading to the formation of coronamic acid from L-alloisoleucine does not involve the loss of nitrogen and (3) the incorporation of (4-$\sp2$H$\sb1$,5-$\sp2$H$\sb1$)-($\pm$)-coronamic acid provides some experimental evidence in support of the hypothesis that coronamic acid and coronafacic acid are biosynthesised separately and coupled by the formation of an amide bond to give coronatine. Polyoximic acid (8) (Fig 4) is the amino acid component of polyoxins A, F, H, I, and K, a unique class of antifungal antibiotics elaborated in the fermentation broths of Streptomyces cacaoi var. $asoensis.\sp{20,22,37}$ Our investigations presented in this dissertation on the biosynthetic origin of polyoximic acid by the administration of specifically labeled precursors to Streptomyces cacaoi var. asoensis (ATCC # 19094) suggest that: (1) polyoximic acid is biosynthetically derived from L-isoleucine, (2) the incorporation of the $\sp{13}$C label from (1-$\sp{13}$C)-L-alloisoleucine into C-1" of polyoximic acid requires that the formation of the exocyclic double bond of polyoximic acid be formed by a syn-elimination of hydrogen from C-3 and not an anti-elimination as previously reported$\sp{38}$ and (3) the retention of two deuterium atoms, at C-4" of polyoximic acid derived from (6-$\sp{13}$C,$\sp2$H$\sb3$)-DL-isoleucine and (6-$\sp{13}$C,$\sp2$H$\sb3$)-DL-alloisoleucine, indicates that the cyclisation reaction requires the loss of only one hydrogen atom from L-isoleucine and L-alloisoleucine.

A technique for the elaboration of ene products derived from aldehydes and 2-methoxypropene into glyoxal monoketals 5 has been devised, and some reactions of the resulting aldehydes have been examined. This methodology should resolve some difficulties encountered in the course of an ongoing total synthesis of phyllanthocin. Key phases of the present study involve oxidation of ether 1, readily available from butyraldehyde through a novel ene-type reaction discovered in our laboratory, using mCPBA and methanol to give a cyclic ketal 2. The resulting seven-membered ring was opened by ketal exchange with 1,3-propanethiol to give thioketal diol 3. Benzylation of the diol proceeded with complete selectivity for the primary alcohol, permitting differentiation of the diol functionality. Protection of the secondary alcohol as a MOM derivative and subsequent ketal exchange with bis(trifluoroacetoxy)iodobenzene reinstated the dimethoxy ketal. Debenzylation under Birch conditions released the free primary alcohol 4, Swern oxidation of which yielded the desired aldehyde 5.* ftn*Please refer to the dissertation for diagrams.

Photochemical reactions between benzoquinones and alkylidenecyclohexanes proceed regioselectively. Regioselectivity is determined by the conformational properties of the cyclic olefin. Photocycloadducts thus obtained may be used for the construction of important alkaloidal frameworks in synthetically useful yields. Oxetane formation is likely to occur through concerted collapse of an exciplex that possesses considerable charge transfer character.

The photolysis of vicinal azoazoxy compound 20 gave azo-side extrusion of N$\sb2$ and formation of azoxy products resulting from radical disproportionation and recombination. Photolysis of vicinal bisazoxy compound 21 resulted in deoxygenation to 20 and vicinal bisazo compound 9B. The $190\sp\circ$C thermolysis of 20 yielded a mixture of products from C-C and C-N homolysis, with a $\Delta\rm G\ddagger$ of 34.8 kcal $\rm mol\sp{-1}.\ \Delta G\ddagger\sb{C-C}$-$\rm\Delta G\ddagger\sb{C-N}$ is calculated to be approximately 2.4 kcal mol$\sp{-1}$ and 1.0 kcal mol$\sp{-1}$ with and without 9,10-dihydroanthracene, respectively. Thermolysis of 21 and azoxy-tert-butane at $190\sp\circ$C resulted in decomposition at the azoxy functionality by a non-radical process similar to the Cope amine oxide pyrolysis. No products of C-C homolysis were seen in the thermolysis of 21.

The synthesis of the azoalkane precursor 21 was accomplished through a Diels-Alder route. This precursor provided a clean and convenient source of the 1,3-biradical 13 upon photolysis. Determination of the product ratio from the triplet biradical by gas chromatographic analysis yielded the rate of intersystem crossing of the biradical from the triplet to the singlet energy state. Structure confirmation of the cyclopropyl ring opening product was accomplished through co-injections of photolysis product and an authentic sample on two different GC columns. The lifetime of 13T was found to lie in the range of 0.4 ns to 18 ns. Comparison of this value to that of 6, whose lifetime is 59 ns, confirms that gem-dimethyls have the effect of increasing the intersystem crossing rate.

The photochemistry of a number of azocyclopropanes has been studied: cis-1-(methyl-trans-azo)-2-phenylcyclopropane, trans-10(methyl-trans-azo)-2-phenylcyclopropane, trans-azocyclopropane and cis-azocyclopropane. Direct irradiation into the lowest n $\rightarrow\pi$* band led to nearly exclusive cis-trans isomerization of the azo group. Minor processes for the phenylcyclopropanes were cyclopropyl ring isomerization, rig expansion of 1-methyl-5-phenyl-2-pyrazoline and formation of styrene. These processes suggest formation of a biradical intermediate which is apparently not formed in the case of trans- and cis-azocyclopropane. Singlet sensitization of cis-1-(methyl-trans-azo)-2-phenylcyclopropane with benzene increased the quantum yields of the processes competing with azo group isomerization. The increased efficiencies indicate that the second excited state of the azoalkane contributed to the observed photochemistry. On the other hand, the second excited state of trans- and cis-azocyclopropane is not accessible to benzene singlet sensitization and so led to exclusive interconversion of the two azo isomers. Direct irradiation into the short wavelength UV band of trans- and cis-azocyclopropane in pentane produced more decomposition products than n $\rightarrow\pi$* excitation. The efficiency of trans $\rightarrow$ cis azo group isomerization decreased at the expense of the C-N and cyclopropyl C-C homolyses. These two cleavages accounted for a large number of products including nitrogen, cyclopropane, ethylene and 1-cyclopropyl-2-pyrazoline. Cyclopropyl ring cleavage to a biradical intermediate followed by reclosure to regenerate the starting azoalkane was postulated as one of the major processes to rationalize the low quantum yield of products. Formation of products propene, allylcyclopropane and 1,5-hexadience upon irradiation at 193 nm suggested production of vibrationally excited cyclopropyl radicals which rearrange to allyl. Short wavelength irradiation of trans-azocyclopropane in the vapor phase led to a large number of decomposition products. Triplet-sensitization of cis-1-(methyl-trans-azo)-2-phenylcyclopropane produced both azo and cyclopropyl group isomerization products, but not styrene. The differing product distribution relative to direct irradiation indicates that the triplet state is not exclusively involved in the singlet photochemistry. The unusually high quantum yield found for triplet-sensitized isomerization of trans-azocyclopropane to the cis isomer was initially rationalized in terms of cyclopropyl ring cleavage to form a biradical intermediate. However, a stereospecifically labelled deuterium analog of trans-azocyclopropane, prepared to test the biradical hypothesis, showed that a such an intermediate is probably not formed upon triplet sensitization.

Part I. The radical chemistry of geminal bis-azoalkanes. Two geminal bis-azoalkanes have been employed to generate carbon centered radicals adjacent to azo substituents. The activation free energies for C-N bond homolysis of 2,2-bis-(phenylazo)propane (1) and 2-methylazo-2-phenylazopropane (2) were 8 kcal/mol lower than for the corresponding model compounds 3-methyl-3-phenylazo-1-butene (4) and 3-methyl-3-methylazo-1-butene (5). This large rate enhancing effect of an $\alpha$-phenylazo substituent is ascribed to the high energy of azo functional groups. 2-(Phenylazo)-2-propyl radical was easily trapped by good hydrogen donors such as thiophenol to afford a hydrazone. The interconversion of geminal bis-azoalkane 2 and tetrazene 3 by low temperature photolysis has been observed. Part II. The radical chemistry of vicinal bis-azoalkanes. Three vicinal bis-azoalkanes have been synthesized by oxidation of hydrazones. In thermolysis, substituents on the azo group dramatically influence the bond homolysis pattern, which varies from pure C-C homolysis when the substituent is phenyl to pure C-N homolysis in the case of a t-butyl substituent. Phenylazo accelerates $\beta$ C-C bond homolysis by approximately 3.2 kcal/mol more than the methylazo group. This result supports the delocalized $\pi$ electronic structure of the 2-(phenylazo)-2-propyl radical. The photochemical behavior of vicinal bis-azoalkanes resembles that of mono azoalkanes except for 9, which underwent both C-C and C-N bond homolysis. $\beta$-Azo radicals from stepwise C-N bond homolysis have been clearly trapped. Part III. Homolysis of a weak C-C bond. The formal para-recombination product of 2-methoxycarbonylpropyl and trityl radicals (53) was readily air oxidized to hydroperoxide through a radical chain mechanism. The weak C-C bond in 53 was cleaved homolytically in thermolysis, photolysis, and triplet sensitized photolysis generating methyl isobutyrate radical and triphenylmethyl radical. This result rules out McElvain's concerted thermolysis mechanism. Triphenylmethyl radical underwent intramolecular cyclization under the photolysis conditions. The facile aromatization of 53 through a radical mechanism was observed.