Two approaches to the tricyclic core of the furanoeremophilane
sesquiterpenoids are described. The first approach entails a projected Diels-Alder/retro Diels-Alder reaction of an acetylenic oxazole 64. Construction of
the pivotal aldehyde 67 commenced from ketone 68. The acetyenic moiety
was then introduced via a Felkin-Ahn addition of lithiopropyne to aldehyde 67.
The final conversion of the cyclohexanone 83 to the acetylenic triflate 65 was
unsuccessful. Attempts at addition of lithiated 2-methyloxazole 88 to ketone 83
were also unsuccessful.
The second approach exploited a new annulation strategy. The
aldehyde 64 was advanced to the 2, 4, 6-triisopropylbenzene
sulfonylhydrazone 102 and a Shapiro reaction of 102 then provided alcohol
96. The furyl stananne 114 was readily prepared via a six-step sequence from
acetylacetaldehyde dimethyl acetal 106. Unification of allylic bromide 90 and
stannane 114 was accomplished through a Stille cross coupling methodology
and the resulting product 113 was advanced to the aldehyde 116. However,
attempts at further oxidation of this aldehyde to the required acid 89 failed. An
alternative furyl stananne 124 with a tert-butyldimethylsilyl substituent at the
C2 position was prepared from 3-furoic acid. An analogous sequence to that
used with 113 led to aldehyde 131 which was successfully cyclized with the
aid of trimethylsilyl trifluromethanesulfonate and 2, 6-lutidine to the tricyclic
structure 132. Oxidation of the epimeric mixture of alcohols, followed by
stereoselective reduction and removal of the tert-butyldimethylsilyl group from
alcohol 134, gave (±)-6β-hydroxyeuroposin (4). Oxidation experiments with
134 were shown to convert the furan in this structure to a butenolide
characteristic of the eremophilenolides. / Graduation date: 2004
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/30482 |
| Date | 13 January 2004 |
| Creators | Shanmugham, Meenakshi Sundaram |
| Contributors | White, James D. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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