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.

Do Methods Matter In Global Leadership Development? A Mixed-Methods Study Of A U.s.-Based International Mba Program

As world communication, technology, and trade become increasingly integrated through globalization, multinational corporations seek employees with global leadership experience and skills. However, the demand for these skills currently outweighs the supply. Given the rarity of globally ready leaders, global competency development should be emphasized in higher education programs. The reality, however, is that university graduate programs are often outdated and focus mostly on cognitive learning. Global leadership competence requires moving beyond the cognitive domain of learning to create socially responsible and culturally connected global leaders. This requires attention to development methods; however, limited research in global leadership development methods has been conducted. A new conceptual model, the global leadership development ecosystem, was introduced in this study to guide the design and evaluation of global leadership development programs. It was based on three theories of learning and was divided into four development methodologies. This study quantitatively tested the model and used it as a framework for an in-depth examination of the design of one International MBA program. The program was first benchmarked, by means of a qualitative best practices analysis, against the top-ranking IMBA programs in the world. Qualitative data from students, faculty, administrators, and staff was then examined, using descriptive and focused data coding. Quantitative data analysis, using PASW Statistics software, and a hierarchical regression, showed the individual effect of each of the four development methods, as well as their combined effect, on student scores on a global leadership assessment. The analysis revealed that each methodology played a distinct and important role in developing different competencies of global leadership. It also confirmed the critical link between self-efficacy and global leadership development.