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Chemical synthesis of structurally complex and biologically active natural products plays a critical role in bridging innovative synthetic methodologies with real world applications, particularly in medicinal fields. However, limited availability of many natural products impedes further studies of their biological activities and possible therapeutic utilization. Synthetic strategies for natural products have the potential to mitigate their scarcity and, at the same time, provide new insights into complex molecules and their practical uses. This dissertation features the synthetic developments of three natural products: thalassospiramide C, anatoxin-a, and xestospongins. The syntheses of these natural products are widely impactful: while thalassospiramide C and xestospongins are marine natural products with promising clinical significance for drug developments, isotopically labeled anatoxin-a is a key to developing a precise quantification analysis for toxins in fresh water. The first chapter of this dissertation focuses on the total synthesis of the N-desmethyl thalassospiramide C, a first in the family of thalassospiramides natural products. Moreover, its mode of binding was elucidated by the crystallography adduct of N-desmethyl thalassospiramide C with cathepsin K. The great inhibitory activity of thalassospiramides against cysteine proteases was clearly depicted through a covalent addition of cysteine residue to the α,β-unsaturated amide of the macrocycle. Our successful chemical synthesis allowed further evaluation of the bioactivities of this macrocyclic cysteine protease inhibitor and addressed the unique 12-membered depsipeptide macrocyclic core as a pharmacophore unit. The second chapter highlights the asymmetric total synthesis of (+)-[13C4]-anatoxin-a, the first isotopically labeled synthesis for this commonly found freshwater cyanotoxin. Two enantioselective synthetic approaches were introduced: a route centered around retaining the enantiopurity of materials established through a Sharpless asymmetric epoxidation of an early-stage allylic alcohol, and an approach employing a penultimate enantioselective intramolecular cyclization allowed for late-stage stereocontrol. The paramount aza-Morita–Baylis–Hillman cyclization strategically maneuvered a dynamic kinetic resolution of cyclic iminiums to construct the bicyclic core of anatoxin-a. Our novel and robust synthesis demonstrated high scalability, and the successful isotopically labeled synthesis allows for a more precise anatoxin-a quantification method to be established. The last chapter of this dissertation describes an ongoing study towards a 2nd generation large-scale synthesis of xestospongin-type natural products, a family of marine alkaloid with promising cancer therapeutics. Two key early-stage intermediates were identified as targets for synthesis optimizations—the α-alkoxy acid intermediate and the common azidoalcohol intermediate responsible for a non symmetrical synthetic design. Optimized routes for both intermediates showcased synthetic efficiencies, with the synthesis of the azidoalcohol featuring a titanium–salalen catalyzed asymmetric epoxidation with hydrogen peroxide of a typically challenging terminal and non-conjugated olefin intermediate. The accomplished shortened and greater yielding synthetic routes for the two intermediates ensures the overall scalability and synthetic ease for the ultimate synthetic access of various xestospongins.

Senior thesis on muon spin relaxation study of LiHoXY1-XF4 and semi-adiabatic specific heat experiment on LiTb0.40Y0.60F4

According to social identity theory, people want to maintain a positive social identity and associate with positive stereotypes related to their social group. Despite the seemingly beneficial effects of a positive stereotype, research has shown that people can be susceptible to both positive and negative stereotypes, defined as stereotype susceptibility, such that people perform in a manner that is consistent with the stereotype. This effect has been shown repeatedly with stereotypes that are very common or well-known. Recently, Schmader (2002) found that this effect was moderated by level of social identity, such that those who were more identified with their social group were more vulnerable to the effects of negative stereotypes than those who were less identified. However, the role of social identity on susceptibility to positive stereotypes and strength of positive stereotype (how well-known the stereotype is) have not been explored. One of the most common positive stereotypes is the perception of Asian Americans as being particularly good at math. Experiment 1 and Experiment 2A showed a significant interactive effect of race prime and race identity on math test performance among Asian Americans. Specifically, high-identified Asian Americans showed a boost in their math test performance when their race is primed relative to those in the no-race prime condition. However, low-identified Asian Americans showed a decrease in math performance under the race prime condition. Motivation seems to provide a partial explanation for the results (Experiment 2A). Specifically, high-identified Asian Americans performed well because they were more motivated to live up to the stereotype as a function of maintaining their positive racial identity. However low-identified Asian Americans were less motivated to live up to the stereotype because their self-definition was not attached to their Asian American identity, and subsequently they performed more poorly. Another moderating factor on stereotype susceptibility effects was stereotype strength. Experiment 2B examined a less well-known stereotype (women and the positive stereotype that they have strong verbal skills) and found that the interaction between gender identity salience and gender identification did not predict women's verbal test performance. Implications and future directions for research on stereotype susceptibility are discussed.