Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.628783
Title: A synthetic approach to determine the stereochemistry of diepomuricanin A
Author: Geesi, Mohammed
ISNI:       0000 0004 5347 1906
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2014
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Abstract:
The total synthesis of bis-epoxide acetogenin, diepomuricanin, has been investigated in order to determine the absolute stereochemistry within the bis-epoxide region. Two approaches (linear and tethered-metathesis) were attempted. In the linear approach, two routes were investigated. In the first one an intermediate aldehyde 248 was created in six steps in order to investigate the asymmetric α-oxidation and diastereoselective additions of organometallic reagents. Model studies using octanal met with moderate success, and highlighted the sensitivity of the α-oxidation products. The instability of the α-oxidation products prevented a proper study of the additions of Grignard and organozinc reagents. In a second route, hydrolytic kinetic resolution of terminal epoxides was investigated in order to obtain optically enriched 1,2-diols suitable for elaboration to diepomuricanins. A revised, convergent approach to diepomuricanin A stereoisomers was developed based on a silicon-tethered metathesis of allylic alcohol fragments. Sharpless asymmetric kinetic resolution (SAKR) of allylic alcohols (±)-305 and (±)-306 was the key step towards the left hand fragments (19S,20S)-302, and (19R,20R)-302, and the right hand fragments (15S,16S)-303, and (15R,16R)-303. Combining them together via a tethered alkene metathesis, led to the key siloxytriene 308. An investigation of the Alder-ene reactions of right hand fragment (15S,16S)-303 display the low selectivity of the less hindered and more electron-rich C27-C28 doble bond. Therefore, the route was modified to proceed by new right hand fragment epoxyalcohols (15S,16S)-354, and (15R,16R)-354, which allowed formation of butenolide 363 towards the synthesis of the diepomuricanin A stereoisomer (anti-5d).
Supervisor: Brown, Richard Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.628783  DOI: Not available
Keywords: QD Chemistry
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