| Summary: | <p>Apratoxin D, recently isolated from two species of cyanobacteria, L. majuscula and L. sordida, exhibits highly potent in vitro cytotoxicity against H-‐‑460 human lung cancer cells with an IC50 value of 2.6 nM. The potent biological activity exhibited by apratoxin D combined with its intriguing molecular architecture has led to the pursuit of its asymmetric total synthesis. Studies toward and completion of the first asymmetric total synthesis of apratoxin D are reported. Key transformations include a Kelly thiazoline formation, Paterson anti-‐‑aldol and an Evans syn-‐‑aldol. The synthesis was completed in 2.1% total yield over 31 steps from (R)-‐‑citronellic acid.</p><p>Cationic gold (I) complexes are highly efficient catalysts for the cycloisomerization of 1,6-‐‑enynes, a transformation capable of providing a great amount of structural complexity from simple starting materials. The in situ spectroscopic analysis of the catalytic cycloisomerization of a 7-‐‑phenyl-‐‑1,6-‐‑enyne, as well as the tandem gold/silver-‐‑catalyzed cycloaddition/hydroarylation of 7-‐‑aryl-‐‑1,6-‐‑enynes is described. The cycloaddition/hydroarylation reaction provides 6,6-‐‑ diarylbicyclo[3.2.0]heptanes in good yield under mild conditions. Experimental observations point to a mechanism involving gold-‐‑catalyzed cycloaddition followed by silver-‐‑catalyzed hydroarylation of a bicyclo[3.2.0]hept-‐‑1(7)-‐‑ene intermediate.</p><p>The control of bond scission and formation by mechanocatalysis has potential in a variety of applications, including biomedical devices, mechanical sensors and self-‐‑</p><p>6</p><p>healing materials. The synthesis and study of C2-‐‑symmetric bis(phosphine) ligands with applications toward mechanocatalysis is described. Additionally, the synthesis and study of a tetradentate ligand designed toward mechanochemical activation of a latent catalytic complex is reported. These studies have allowed further development in the design of transition metal complexes capable of activation by mechanical force.</p> === Dissertation
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