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A synthetic approach to klaineanone and tandem radical cyclisations in the synthesis of lysergic acid

A synthetic approach to klaineanone and tandem radical cyclisations in the synthesis of lysergic acid
A synthetic approach to klaineanone and tandem radical cyclisations in the synthesis of lysergic acid

A brief introduction to quassinoids and the retrosynthetic analysis of klaineanone is described in chapter one. A carbene insertion reaction of 3,5-dimethyl-4-methylene-3-(3-diazo-3-methoxycarbonyl-2-oxopropyl)-1-cyclohexanone, 1-ethylene acetal was successful giving the tricycle 8,8-ethylenedioxy-3-methoxycarbonyl-6,10-dimethyl-4-oxotricyclo [4.4.0.01.3]decane. Robinson annulation failed, but a successful Wichterle reaction to give 8,8-ethylenedioxy-3-carbomethoxy-6,10-dimethyl-5-[1-(3-chloro-2-butenyl)]-4-oxotricyclo [4.4.0.01,3] decane, an intermediate in a projected synthesis of klaineanone is described in chapter two.

In chapter three, an introduction to ergot alkaloids and a brief summary of the synthetic efforts made in this field is described. A novel free radical cyclisation approach for the synthesis of lysergic acid analogues has been investigated. Synthesis of fragments of the proposed route is described in chapter four.

The homolytic cleavage of carbon-bromine bond, mediated by tri-n-butyltin hydride, led to the development of a novel way for the construction of 3,4-disubstituted dihydroindoles via single cyclisation; hexahydrobenz[cd]indoles via double tandem cyclisation and both octahydroindolo[6,5,4-cd]indoles and decahydroindolo[4,3-fg] quinolines via triple radical cyclisation.

A successful tandem double 5-exo-trig,6-endo-trig cyclisation of aryl radical produced from N-3-[3-(N-acetyl-N-allylamino)-2-bromophenyl]-5-(carbomethoxy)-1,4,5,6-tetrahydro -N-methylpyridine to afford methyl 1-acetyl-2,3,9,10-tetrahydrolysergate is described in chapter five.

In chapter six, unsuccessful attempts to synthesise dihydrolysergic acid, to establish methods for introducing a 9,10-double bond in the ring D of ergot alkaloids after tandem radical cyclisation and some further ideas for future work are described.

University of Southampton
Özlü, Yusuf
Özlü, Yusuf

Özlü, Yusuf (1993) A synthetic approach to klaineanone and tandem radical cyclisations in the synthesis of lysergic acid. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

A brief introduction to quassinoids and the retrosynthetic analysis of klaineanone is described in chapter one. A carbene insertion reaction of 3,5-dimethyl-4-methylene-3-(3-diazo-3-methoxycarbonyl-2-oxopropyl)-1-cyclohexanone, 1-ethylene acetal was successful giving the tricycle 8,8-ethylenedioxy-3-methoxycarbonyl-6,10-dimethyl-4-oxotricyclo [4.4.0.01.3]decane. Robinson annulation failed, but a successful Wichterle reaction to give 8,8-ethylenedioxy-3-carbomethoxy-6,10-dimethyl-5-[1-(3-chloro-2-butenyl)]-4-oxotricyclo [4.4.0.01,3] decane, an intermediate in a projected synthesis of klaineanone is described in chapter two.

In chapter three, an introduction to ergot alkaloids and a brief summary of the synthetic efforts made in this field is described. A novel free radical cyclisation approach for the synthesis of lysergic acid analogues has been investigated. Synthesis of fragments of the proposed route is described in chapter four.

The homolytic cleavage of carbon-bromine bond, mediated by tri-n-butyltin hydride, led to the development of a novel way for the construction of 3,4-disubstituted dihydroindoles via single cyclisation; hexahydrobenz[cd]indoles via double tandem cyclisation and both octahydroindolo[6,5,4-cd]indoles and decahydroindolo[4,3-fg] quinolines via triple radical cyclisation.

A successful tandem double 5-exo-trig,6-endo-trig cyclisation of aryl radical produced from N-3-[3-(N-acetyl-N-allylamino)-2-bromophenyl]-5-(carbomethoxy)-1,4,5,6-tetrahydro -N-methylpyridine to afford methyl 1-acetyl-2,3,9,10-tetrahydrolysergate is described in chapter five.

In chapter six, unsuccessful attempts to synthesise dihydrolysergic acid, to establish methods for introducing a 9,10-double bond in the ring D of ergot alkaloids after tandem radical cyclisation and some further ideas for future work are described.

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Published date: 1993

Identifiers

Local EPrints ID: 462409
URI: http://eprints.soton.ac.uk/id/eprint/462409
PURE UUID: 440770bf-57cc-4991-8119-ad17a8563981

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Date deposited: 04 Jul 2022 19:07
Last modified: 04 Jul 2022 19:07

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Author: Yusuf Özlü

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