Towards a total synthesis of trichodermal and colodendrolide via a common key intermediate
Towards a total synthesis of trichodermal and colodendrolide via a common key intermediate
The synthesis of trichodermol (2) was investigated. The A-ring was formed by Diels-Alder reactions, which produced (2-furoyl) substituted cyclohexenes (30) and (36) with the tertiary methyl in its required position. The high yielding adduct (36) was prepared because of the low yield of adduct (30). Problems were encountered in trying to obtain a 1,3-hydroxyketone; even a protected alcohol α to a silylenol ether eliminated readily to form the enone. Consequently the 1,3-diol (59), with two of the methyls in position, was obtained by epoxidation of the enone (40), followed by reduction of the alkene and then the epoxyketone. The rest of the molecule was to be formed by elaboration of ring opened furfuryl or furanyl derivatives. In the event these gave rise to either benzofuran (33), (60) or 6-(cyclohexenyl)-pyran-2,5-dione compounds (41), rather than the sought after benzopran. The methodology for preparing furoyl substituted cyclohexenes was also applied to a model study of the synthesis of calodendrolide (65). The ketones (92) and (102), with both the vinyl and tertiary methyls in place, were readily converted to acetoxy derivatives functionalised in the 2-position, (98), (100), (104) and (105), by reduction and then esterification. All three alcohol protection-deprotection systems investigated failed; trimethylsilyl was too labile and both tert-butyl dimethylsilyl and tetrahydro-2H-pyran presented removal problems.bf 40-1019, 40-1020 withdrawn.
University of Southampton
1989
Johnson, Susan Debra
(1989)
Towards a total synthesis of trichodermal and colodendrolide via a common key intermediate.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The synthesis of trichodermol (2) was investigated. The A-ring was formed by Diels-Alder reactions, which produced (2-furoyl) substituted cyclohexenes (30) and (36) with the tertiary methyl in its required position. The high yielding adduct (36) was prepared because of the low yield of adduct (30). Problems were encountered in trying to obtain a 1,3-hydroxyketone; even a protected alcohol α to a silylenol ether eliminated readily to form the enone. Consequently the 1,3-diol (59), with two of the methyls in position, was obtained by epoxidation of the enone (40), followed by reduction of the alkene and then the epoxyketone. The rest of the molecule was to be formed by elaboration of ring opened furfuryl or furanyl derivatives. In the event these gave rise to either benzofuran (33), (60) or 6-(cyclohexenyl)-pyran-2,5-dione compounds (41), rather than the sought after benzopran. The methodology for preparing furoyl substituted cyclohexenes was also applied to a model study of the synthesis of calodendrolide (65). The ketones (92) and (102), with both the vinyl and tertiary methyls in place, were readily converted to acetoxy derivatives functionalised in the 2-position, (98), (100), (104) and (105), by reduction and then esterification. All three alcohol protection-deprotection systems investigated failed; trimethylsilyl was too labile and both tert-butyl dimethylsilyl and tetrahydro-2H-pyran presented removal problems.bf 40-1019, 40-1020 withdrawn.
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Published date: 1989
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Local EPrints ID: 461598
URI: http://eprints.soton.ac.uk/id/eprint/461598
PURE UUID: 461df868-061b-4659-a892-d8fba036a1f3
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Date deposited: 04 Jul 2022 18:50
Last modified: 04 Jul 2022 18:50
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Author:
Susan Debra Johnson
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