The Lewis acid catalysed tandem Michael-Claisen (4C + 2C) annelation reaction of 1-trimethylsiloxy-1-methoxy-3-phenylthio-1,3-butadiene and 4,4-dimethyl-2-cyclohexen-1-one has been reexamined. The intermediate E and Z Michael adducts were cyclized under basic conditions to give the $ beta$-diketone 3-phenylthio-5,6,4a,8a-tetrahydro-5,5-dimethyl-(4H,7H)-naphthalen-1,8-dione. Angular methylation of this $ beta$-diketone under basic conditions was examined in detail, providing the cis angularly methylated product stereoselectively. / The cis ring junction stereochemistry of the $ beta$-diketone derivative mentioned above has been used advantageously to establish the C$ sb8$ (naphthalene numbering) $ alpha$-hydroxyl stereochemistry required for the forskolin structure. A subsequent enolate oxidation/nucleophilic addition sequence was then used to stereoselectively install the C$ sb1$ and C$ sb2$ (naphthalene numbering) cis $ alpha, alpha$-diol functionality also present in the forskolin structure. Subsequent functional group manipulations then provided 1,2,5,6,7,8,8a-heptahydro-$1 alpha,2 alpha$,4-${ rm trihydroxy}$-8$ alpha$-(tert-butyldimethylsiloxy)-$1 beta(1 sp prime$-${ rm hexynyl}$)-2,5,5,8a$ beta$-tetramethyl-naphthalen-3-one, a highly oxygenated $ alpha$-diketone intermediate for the synthesis of forskolin. / A number of the decalin compounds leading to the $ alpha$-diketone intermediate mentioned above, were tested for antifeedant activity against the spruce budworm (Choristoneura fumiferana). Eleven of these compounds were found to be active and structure-activity relationships were examined.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.39396 |
| Date | January 1992 |
| Creators | Guertin, Kevin Richard |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001316879, proquestno: NN80338, Theses scanned by UMI/ProQuest. |
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