Towards the total synthesis of amphidinolide C

Yang, Guang (2013) Towards the total synthesis of amphidinolide C. PhD thesis, University of Glasgow.

Abstract

Amphidinolide C is a macrolactone possessing two trans-2,5 substituted tetrahydrofurans embedded in the ring, isolated from the inner cells of acoel flatworms that live on algae and seaweed in the coral reefs of Okinawa. Amphidinolide C possesses complex molecular architecture and this combined with its potent biological activity make it an alluring target for synthesis.
Herein, is presented the convergent synthetic route towards the total synthesis of amphidinolide C, including the enantioselective total synthesis of two key intermediates C1–C17 and C18–C34 fragments.
The key transformations in the synthetic route of C1–C17 fragment include intramolecular conjugate addition of an oxygen nucleophile to obtain the trans-2,5 tetrahydrofuran (C1–C8 subunit), stereoselective boron-mediated aldol condensation, E-selective HWE olefination of a ketone followed by regioselective hydrostannylation of an enyne to give the desired diene system. Lastly, C1–C17 fragment was complete by nucleophilic addition of aldehyde with a vinylic anion.
Important features of the synthesesis of the C18–C34 fragment include kinetic resolution under Sharpless asymmetric epoxidation conditions to furnish the enantionmericly pure alcohol, Sonogashira coupling followed by Red-Al reduction of the enyne system to obtain the E,E-diene system.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Synthesis of the C1–C17 Fragment of Amphidinolides C, C2, C3 and F. J. Stephen Clark, Guang Yang, and Andrew P. Osnowski Org. Lett. 2013, 15, 1460. DOI: 10.1021/ol400482j Synthesis of the C18–C34 Fragment of Amphidinolides C, C2, and C3. J. Stephen Clark, Guang Yang, and Andrew P. Osnowski Org. Lett. 2013, 15, 1464. DOI: 10.1021/ol4004838
• Keywords: Amphidinolide, total synthesis
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Clark, Prof. J. S.
• Date of Award: 2013
• Depositing User: Mr Guang Yang
• Unique ID: glathesis:2013-4305
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 May 2013 08:22
• Last Modified: 07 Mar 2014 11:13
• URI: https://theses.gla.ac.uk/id/eprint/4305