The first enantioselective oxidative rearrangement of indoles to spirooxindoles was developed. A 2,3-disubstituted indole was stereoselectively epoxidized using an in situ-generated chiral dioxirane catalyst. Rearrangement of the transient epoxide intermediate afforded the antipode of the tricyclic spirooxindole present in the marine alkaloid citrinadin A.
A mild and rapid entry to 1,4-dioxygenated xanthones from benzocyclobutenones was developed. This method was applied to the construction of the highly aromatic pentacyclic core of IB-00208, a promising antitumor agent with reported nanomolar activity. The requisite angularly-fused benzocyclobutenone was accessed via a novel ring-closing metathesis approach. Lack of success in synthesizing the final ring of IB-00208 from the pentacycle led us to revise our approach and incorporate an extra ring earlier in the synthesis. After constructing a modified benzocyclobutenone, the hexacyclic core of IB-00208 was efficiently accessed using the same key chemistry. An oxidation, deprotection and glycosylation remain to complete the synthesis of the natural product.
A total synthesis of antimicrobial and antineoplastic cribrostatin 6 was accomplished in only four steps in the longest linear sequence from commercially available starting materials. The key step employed a tandem 4π-electrocyclic ring opening, radical cyclization, and homolytic aromatic substitution sequence to afford the tricyclic core of the natural product, which was converted to cribrostatin 6 via a subsequent oxidation in one pot. The versatility of this reaction sequence was demonstrated by preparation of analogs of the natural product, which were tested for their anticancer activity. / text
| Identifer | oai:union.ndltd.org:UTEXAS/oai:repositories.lib.utexas.edu:2152/ETD-UT-2010-05-944 |
| Date | 01 October 2010 |
| Creators | Knueppel, Daniel Isaiah |
| Source Sets | University of Texas |
| Language | English |
| Detected Language | English |
| Type | thesis |
| Format | application/pdf |
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