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Title: Studies towards the total synthesis of the amphidinolide C family of natural products
Author: Osnowski, Andrew P.
ISNI:       0000 0004 2750 6239
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2013
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The amphidinolide compounds represent an extensive array of marine natural products, a number of which demonstrate potent anti-cancer bioactivity in vitro. Amphidinolide C represents an attractive synthetic target due to a combination of potent bioactivity and complex molecular architecture. This project deals with a modular and convergent total synthesis approach to amphidinolide C from which two synthetic fragments of similar size and complexity, termed ‘northern’ and ‘southern’, were synthesised in a stereoselective fashion. The stereochemical commonality between the branched chains of the 2,5-trans tetrahydrofuran systems found within both fragments, led to the conclusion that a keystone common intermediate could be applied to the synthesis of each. Previous efforts within the group have shown that 2,5-trans tetrahydrofuran-3-ones could be prepared through a diastereoselective rearrangement of a free or metal-bound oxonium ylide generated from a metal carbenoid. This thesis details the scalable preparation of the intermediate tetrahydrofuranone through tandem oxonium ylide and [2,3]-sigmatropic rearrangement. Subsequent discussions show the applicability of the intermediate to forming the C-(18)—C-(34) fragment of amphidinolide C and the C-(18)—C-(29) fragment of amphidinolide F, through the use of palladium cross-coupling methodology; alternative methods found to prepare the ‘northern’ fragment are also discussed. Additionally, the C-(1)—C-(8) fragment was prepared from the common intermediate system, the key steps in this synthesis involved introduction of the C-(4) methyl group through homogeneous catalytic hydrogenation and Luche reduction to afford the C-(7) alcohol.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry