Source: Dissertation Abstracts International, Volume: 79-05(E), Section: B.

Adviser: Seth B. Herzon.

Aldehydes, linear alcohols, amines and carboxylic acids are very common functional groups found in bioactive natural products, phainiaceutical reagents and synthetic intermediates. The direct addition of oxygen- or amine-based nucleophiles to teluiinal alkynes in anti-Markovnikov fashion is a powerful strategy to access those functional groups, since terminal alkynes are widely commercially available and synthetically accessible. We have developed a new ruthenium complex 18 that contains the air-stable and readily prepared bipyridine ligand. This catalyst enabled the anti-Markovnikov hydration of the broad range of terminal alkynes under mild conditions such as room temperature. The transformation of terminal alkynes into amines and carboxylic acids through aldehyde intermediates was achieved in one pot by utilizing complex 18. Furthermore, we were able to develop an air-stable and highly-reactive anti-Markovnikov reductive hydration catalyst 28e to obtain linear alcohols in one step from terminal alkynes. Reaction progress kinetic analysis and deuterium labeling studies elucidated three catalytic cycles involved in the reductive hydration with catalyst 28e. *Please refer to dissertation for diagrams.

The mechanistic understanding of the reaction enabled the wide range of substrate scope and successful application to the synthesis of an anti-HIV alkaloid, (+)-batzelladine B.

The diterpenoid natural product (+)-pleuromutilin (47) was first isolated in 1951 from a fungal culture and was found to display antibacterial activity by binding to peptidyl transferase domain of the 50S ribosome subunit. (+)-Pleuromutilin (47) and its derivatives are promising candidates for a new class of antibiotic scaffold. A modular total synthesis will provide a useful tool to re-structure the pleuromutilin core and expand the scope of derivatives. We have developed an enantioselective and modular synthetic route for pleuromutilins. Our synthetic route consists from combining two neopentyl reagents, enimide 213 and alkyl iodide 169 to access ynal 218 for the late stage reductive cyclization. The synthesis of tricyclic compound 219 with the pleuromutilin core was achieved in 11 steps. This route enabled us to access not only (+)-pleuromutilin (47), but also (+)-12-epi-pleuromutilin ( 234), and (+)-11,12-epi-pleuromutilin (237). *Please refer to dissertation for diagrams.