Studies toward the total synthesis of (+)-providencin (1), a highly oxygenated cembranoid dipterpene with a unique bicyclo[12.2.0]hexadecane skeleton and pronounced biological activity, are described. These studies resulted in the synthesis of advanced intermediates 320 and 332 which contain all of the carbon atoms of 1. In a first generation approach toward 1, a zirconium-mediated deoxygenative ring contraction of furanose 177 was used to furnish enantiopure cyclobutanol 176. Olefination of furan aldehyde 197 with phosphonate 214 completed cyclobutylfuran segment 215.
A second generation approach toward cyclobutylfuryl subunit 221 via ring-closing metathesis of diene 237 was unproductive, but the iodolactone subunit 228 needed for 1 was prepared successfully using carbometallation-iodination of alkyne 231. Nucleophilic substitution of tosylate 230 with the dianion of phenylselenyl acetic acid (252) followed by acid-catalyzed lactone formation was employed for construction of the γ-lactone moiety of 228.
A third generation route to the cyclobutylfuryl subunit of 1 involved a tin(II) chloride-mediated stereoselective allenol synthesis by reaction of aldehyde 302 with propargyllic bromide 264. A silver-catalyzed allenone-to-furan isomerization of 309 completed the synthesis of cyclobutylfuran subunit 288. Attempts to couple the two major fragments, 228 and 288, using palladium-catalyzed C-H activation of the furan component were unsuccessful, but linkage of two major subunits was achieved at the C12-C13 bond via an intermolecular aldol reaction to give 332 and at the C6-C7 bond using intermolecular palladium-catalyzed cross-coupling to afford 320. / Graduation date: 2012
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/28075 |
| Date | 16 February 2012 |
| Creators | Jana, Somnath |
| Contributors | White, James D. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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