Synthetic studies towards the avermectins and milbemycins
Synthetic studies towards the avermectins and milbemycins
A synthesis of the hexahydrobenzofuran portion of the avermectins has been developed. In a model study an appropriately substituted vinyl bromide was found to undergo 5-exo-dig, 6-endo-trig radical cyclisation on treatment with tri-n-butyltin hydride. The product underwent in situ 1,6-addition of tri-ni-butyltin hydride, generating an allyl stannane. Treatment of the allyl stannane with a peracid served to introduce the C-7 hydroxyl group. The reaction was extended to a tandem 5-exo-dig, 6-endo-trig cyclisation, thiophenyl radical elimination reaction. This allowed the preparation of the hexahydrobenzofuran portion of the avermectins, containing the C-3, C-4 double bond in an exocyclic position. This will avoid the C-2 epimerisation/conjugation problems of existing routes. Investigations were also carried out upon an avermectin and milbemycin spiroacetal synthesis, involving a hetero Diels-Alder reaction between a silyloxydiene and an aldehyde as a key step. The route revealed some interesting chemistry of 6-substituted-3-hexyn-2-ones.(DX86229)
University of Southampton
1988
Willis, Paul Andrew
(1988)
Synthetic studies towards the avermectins and milbemycins.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
A synthesis of the hexahydrobenzofuran portion of the avermectins has been developed. In a model study an appropriately substituted vinyl bromide was found to undergo 5-exo-dig, 6-endo-trig radical cyclisation on treatment with tri-n-butyltin hydride. The product underwent in situ 1,6-addition of tri-ni-butyltin hydride, generating an allyl stannane. Treatment of the allyl stannane with a peracid served to introduce the C-7 hydroxyl group. The reaction was extended to a tandem 5-exo-dig, 6-endo-trig cyclisation, thiophenyl radical elimination reaction. This allowed the preparation of the hexahydrobenzofuran portion of the avermectins, containing the C-3, C-4 double bond in an exocyclic position. This will avoid the C-2 epimerisation/conjugation problems of existing routes. Investigations were also carried out upon an avermectin and milbemycin spiroacetal synthesis, involving a hetero Diels-Alder reaction between a silyloxydiene and an aldehyde as a key step. The route revealed some interesting chemistry of 6-substituted-3-hexyn-2-ones.(DX86229)
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Published date: 1988
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Local EPrints ID: 460967
URI: http://eprints.soton.ac.uk/id/eprint/460967
PURE UUID: 25f4bc9a-b4f8-47b4-903a-612aae1f67b4
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Date deposited: 04 Jul 2022 18:32
Last modified: 04 Jul 2022 18:32
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Author:
Paul Andrew Willis
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