General Approach to the Synthesis of the Chlorosulfolipids Danicalipin A, Mytilipin A, and Malhamensilipin A in Enantioenriched Form and Progress towards the Synthesis of the Psammaplysin Family of Natural Products
- Author(s): Carlson, Joseph Scott
- Advisor(s): Vanderwal, Christopher D
- et al.
The dissertation describes a second-generation synthesis of three structurally related chlorosulfolipid natural products. Chapter 1 of the dissertation focuses on the discovery and state of the synthetic art of the chlorosulfolipids at the time this work began. Chapter 2 of the dissertation describes the key advances made, include highly stereocontrolled additions to α,β-dichloroaldehydes, kinetic resolutions of complex vinyl epoxide intermediates, and Z-selective cross metatheses of vinyl epoxides.
Chapter 3 of the dissertation describes background information pertaining to the
psammaplysin family of natural products, including their biosynthesis and relevant bioactivity. Also described is the retrosynthetic strategy developed for the synthesis of all members of the psammaplysin family of natural products, featuring a donor-acceptor cyclopropane fragmentation as the key step. Chapter 4 details the exploration of several strategies designed to evaluate the best methods for: incorporation of the secondary stereogenic alcohol, donor-acceptor cyclopropane fragmentation/spirocyclic ring formation, and oximinoamide incorporation. A ketene Diels–Alder disconnection strategy was successful in producing the spirooxepin-isoxazoline ring fusion present in the psammaplysin family of natural products. Also described are preliminary results for incorporation of the stereogenic alcohol at an early stage intermediate that has the potential for being elaborated further using the ketene Diels–Alder strategy.