No description available.

Among Nature's creation, terpenoids are more versatile and exciting compounds, and provide fertile ground for developing and testing new synthetic strategies because of their phenomenal structural diversity. The thesis entitled “Enantiospecific Synthesis of Tetraquinane Diterpenes Crinipellins” describes the first enantiospecific synthesis of norcrinipellin and crinipellins, and the tricyclic core structure of tricycloillicinone, ialibinones, and takaneones. In the thesis, the compounds are sequentially numbered (bold) and references are marked sequentially as superscripts and listed at the end of the thesis. All the spectra included in the thesis were obtained by xeroxing the original NMR spectra. Crinipellins, the first group of natural products to contain a tetraquinane carbon framework, were isolated in 1985 by the research groups of Steglich and Anke from the submerged cultures of the basidiomycete Crinipellis stipitaria. Recently, In 2010, Shen and Li also reported the isolation of four new crinipellins from the Crinipellis stipitaria 113. In the present thesis, first enantiospecific synthesis of norcrinipellin and crinipellins has been described. To begin with, (S)-campholenaldehyde was transformed into the (1R,5R)-7,8,8-trimethylbicyclo[3.3.0]oct-6-en-3-one employing an intramolecular rhodium carbenoid insertion of a diazoketone, which was then transformed into the methyl (1R,2S,6R,8S,10R)-10-methoxy-2-methyl-5-oxotricyclo[6.3.0.02,6]undecane-4-carboxylate via rhodium carbenoid promoted activation of a tertiary methyl group to generate the cis, anti, cis-linear triquinane. The triquinane obtained was then transformed into ethyl 4-[(1R,2S,6S,8S,10R)-10-methoxy-2,5dimethyl-3-oxotricyclo[6.3.0.02,6]undec-4-ene-6-yl]butanoate by a sequence of reactions including an alkylative 1,3-enone transposition, which on intramolecular Michael addition reaction followed by DBU mediated equilibration generated a 5:4 mixture of ethyl (1S,3S,5R,7R,8S,11S,12R) and (1S,3S,5R,7R,8S,11S,12S)-5-methoxy8,11-dimethyl-9-oxotetracyclo[6.6.0.01,11.03,7]tetradecane-12-carboxylates, which were transformed into (12R) and (12S)-15-hydroxy-5-methoxy-20-norcrinipellin-9-ones and (12S) and (12R)-5-methoxy-20-norcrinipell-15-en-9-ones. The methodology has been further modified and extended for the first enantiospecific synthesis of (12R) and (12S) 15-hydroxy-5-(methoxymethoxy)crinipellin-9-ones In 1995, Fukuyama and coworkers reported the isolation of tricycloillicinone from Illicium tashiroi, containing an interesting 3,4,4-trimethyltricyclo[5.3.1.01,5]undecane system. This tricyclic structure was also present in two groups of acylphloroglucinoid natural products, ialibinones and takaneones. An enantiospecific synthesis of the tricyclic core structure of tricycloillicinone, ialibinones, and takaneones have been accomplished starting from (S)-campholenaldehyde employing a transannular RCM reaction as the key step, (S)-Campholenaldehyde was converted into methyl (5R)-6,6,7-trimethyl-3-oxobicyclo[3.3.0]octa-1,7-diene-2-carboxylate via the methyl (1R,5R)-6,6,7-trimethyl-3-oxobicyclo[3.3.0]oct-7-ene-2-carboxylate, which was then transformed into (1R,3S,5S)-3-allyl-7,8,8-trimethyl-5-vinylbicyclo[3.3.0]oct6-en-3-ol containing the vinyl and allyl groups at C-1 and C-3 carbons syn to each other. Transannular RCM reaction of the hydroxy diene led to the tricyclic core structure of tricycloillicinone. Further elaboration of the side chain at C-3 position led to the tricyclic core structure of ialibinones, and takaneones.

2-Pyridones are known to undergo a facile [4+4] photocycloaddition with themselves and other conjugated molecules. These transformations provide an access to complex molecular structures such as highly substituted cyclooctanoid derivatives, which normally represent a significant synthetic challenge. Moreover, the 2-pyridone photoadducts can be further elaborated into various biologically relevant products. The work presented here broadens the horizons of the [4+4] photocycloaddition in two distinct directions: 1) by utilizing [4+4] photocycloaddition in a total synthesis of crinipellin natural products possessing antibiotic and antitumor activity and 2) by developing a novel type of [4+4] photocycloaddition that employs a conjugated enyne as a partner of 2- pyridone. Our approach to the tetraquinane core of the crinipellins features intramolecular [4+4] photocycloaddition of a tethered furan-pyridone molecule followed by a four-step transannular ring closure. The sequence allows for a rapid assembly of a molecular framework by installing 19 of the 20 required carbon atoms and all but two stereogenic centers. The described synthesis represents an interesting new approach to these polycyclic molecules and a way to access crinipellin analogues. The enyne-pyridone [4+4] photocycloaddition led to formation of intriguing 1,2,5-cyclooctatriene-based products. Presence of the allene functionality was used as a lever in exploring the possibilities for derivatization of these photoadducts. Our investigations of enyne-pyridone photocycloaddition have come a long way: from the first proof-of-concept intermolecular trials producing complex mixtures, through the initial investigations of the intramolecular variant that taught us how to direct the reaction to the necessary mode ([2+2] vs. [4+4] photocycloaddition), and eventually to the controlled formation of stable allenic photoadducts and their further transformation into a diverse set of functionalized molecular scaffolds. We found that the inherent kinetic instability of 1,2,5-cyclooctatrienes facilitates several pathways of strain relief: allene-allene [2+2] dimerization, photooxidative decarbonylation when the irradiation is conducted in presence of air, isomerization of the 1,2-diene fragment into a 1,3-diene and the acid-promoted Cope rearrangement. Additionally, enyne-pyridone photoadducts can undergo transannular ring closure when treated with bromine and also be transformed into valuable bicyclo [5.1.0] octane structures that incorporate a rare example of a stable cyclopropanone by a fast and selective epoxidation-rearrangement process. Several important goals were achieved in the described research study. First, strategic incorporation of [4+4] photocycloaddition as one of the key steps in targeted synthesis of natural products has demonstrated the potential of this powerful reaction. Second, an efficient new approach to a tetraquinane skeleton was developed and successfully executed. Third, the fundamental basis for the novel photochemical transformation (enyne-pyridone cycloaddition) was set and major trends for this reaction were established resulting in obtaining stable allenic photoadducts. Finally, chemical properties and reactivity of stabilized amide-bridged 1,2,5-cyclooctatriene photoproducts were investigated breaking the ground for future involvement of these intermediates in synthetic strategies towards biologically active natural products and their analogues. / Chemistry