Novel Photochemical Methodologies For Diversity Oriented Synthesis And Screening Of Combinatorial Libraries

The main goal of this project was to develop an efficient methodology allowing rapid access to structurally diverse scaffolds decorated with various functional groups. Initially, we discovered and subsequently developed an experimentally straightforward, high-yielding photoinduced conversion of readily accessible diverse starting materials into polycyclic aldehydes and their (hemi)acetals decorated by various pendants. The two step sequence, involving the Diels-Alder addition of heterocyclic chalcones and other benzoyl ethylenes to a variety of dienes, followed by the Paternò-Büchi reaction, was described as an alkene-carbonyl oxametathesis. This methodology offers a rapid increase in molecular complexity and diversity of the target scaffolds. To develop this novel methodology further and explore its generality, we directed our attention to the Diels-Alder adducts based on various chromones. We discovered that the Diels-Alder adducts of chromones are capable of photoinduced alkene-arene [2+2] cycloaddition producing different dienes, which can either dimerize or be introduced into a double-tandem [4π+2π]·[2π+2π]·[4π+2π]·[2π+2π] synthetic sequence, followed by an acid-catalyzed oxametathesis, leading to a rapid expansion of molecular complexity over a few experimentally simple steps. In view of the fact that oxametathesis previously was primarily observed in aromatic oxetanes, we decided to prepare model aliphatic oxetanes with a conformationally unconstrained or "flexible" methyl group based on the Diels-Alder adducts of cyclohexadiene or cyclopentadiene with methyl vinyl ketone. Upon addition of an acid, the expected oxametathesis occurred with results similar to those observed in the aromatic series proving the generality of this approach. Also we synthesized polycyclic oxetanes resulting from the Diels-Alder adducts of cyclic ketones. This not only gave us access to remarkably strained oxetane systems, but also the mechanism for their protolytic ring opening provided a great deal of insight to how the strain affects the reactivity. Additionally, we discovered that although the model Hetero-Diels-Alder adducts did not undergo [2+2] cycloaddition, both exo- and endo-Sulfa-Diels-Alder products, nonetheless, were photochemically active and various products with defined stereochemistry could be produced upon photolysis. In conclusion, we have developed an approach to the encoding and screening of solution phase libraries based on the photorelease of externally sensitized photolabile tags. The encoding tags can be released into solution only when a binding event occurs between the ligand and the receptor, equipped with an electron transfer sensitizer. The released tags are analyzed in solution revealing the identity of the lead ligand or narrowing the range of potential leads.

Citation Methodologies in Eusebius’ Historia ecclesiastica and Other Ancient Historiography

This dissertation examines ancient historiographic citation methodologies in light of Mikhail Bakhtin’s dichotomy between polyphony and monologization. In particular, this dissertation argues that Eusebius of Caesarea’s Historia ecclesiastica (HE) abandons the monologic citation methodology typical of previous Greek and Hellenistic historiography and introduces a polyphonic citation methodology that influences subsequent late-ancient Christian historiography to varying degrees. Whereas Pre-Eusebian Greek and Hellenistic historiographers typically use citations to support the single authorial consciousness of the historiographer, Eusebius uses citations to counterbalance his own shortcomings as a witness to past events. Eusebius allows his citations to retain their own voice, even when they conflict with his. The result is a narrative that transcends the point of view of any single individual and makes multiple witnesses, including the narrator, available to the reader. Post-Eusebian late-ancient Christian historiographers exhibit the influence of Eusebius’ innovation, but they are not as intentional as Eusebius in their use of citation methodologies. Many subsequent Christian historiographers use both monologic and polyphonic citation methodologies. Their tendency to follow Eusebius’ practice of citing numerous lengthy citations sometimes emphasizes points of view that oppose the author’s point of view. When an opposing viewpoint surfaces in enough citations, a polyphonic citation methodology emerges. The reader holds the two different narrative strands in tension as the author continues to give voice to opposing viewpoints. After illustrating the citation methodologies with passages from numerous Greek, Hellenistic, and late ancient Christian historiographers, this dissertation concludes with a short computational analysis that uses natural language processing to reveal some broad trends that highlight the previous findings and suggest a possibility for future research.