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A synthetic approach to determine the stereochemistry of diepomuricanin A

A synthetic approach to determine the stereochemistry of diepomuricanin A
A synthetic approach to determine the stereochemistry of diepomuricanin A
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 ?-oxidation and diastereoselective additions of organometallic reagents. Model studies using octanal met with moderate success, and highlighted the sensitivity of the ?-oxidation products. The instability of the ?-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).
Geesi, Mohammed
0a8d23f3-16ca-46c9-a537-e0b5f39009fb
Geesi, Mohammed
0a8d23f3-16ca-46c9-a537-e0b5f39009fb
Brown, Richard
21ce697a-7c3a-480e-919f-429a3d8550f5

Geesi, Mohammed (2014) A synthetic approach to determine the stereochemistry of diepomuricanin A. University of Southampton, Chemistry, Doctoral Thesis, 273pp.

Record type: Thesis (Doctoral)

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 ?-oxidation and diastereoselective additions of organometallic reagents. Model studies using octanal met with moderate success, and highlighted the sensitivity of the ?-oxidation products. The instability of the ?-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).

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Published date: 1 September 2014
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 369347
URI: http://eprints.soton.ac.uk/id/eprint/369347
PURE UUID: 6003817d-4241-45e2-b981-64df6cc1a0d8
ORCID for Richard Brown: ORCID iD orcid.org/0000-0003-0156-7087

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Date deposited: 27 Oct 2014 11:40
Last modified: 06 Jun 2018 13:01

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