Record Details
Total Syntheses of Fastigiatine and the Hibarimicin Aglycons
ScholarsArchive at Oregon State University
| Field | Value |
|---|---|
| Title | Total Syntheses of Fastigiatine and the Hibarimicin Aglycons |
| Names |
Liau, Brian
(creator) |
| Date Issued | 2013 (iso8601) |
| Note | Access restricted to the OSU Community |
| Abstract | Part one of this two-part thesis describes my efforts toward the total syntheses of the complex polycyclic alkaloids himeradine A and fastigiatine, which are members of the Lycopodium family of natural products. A cascade reaction sequence featuring a biosynthesis-inspired transannular Mannich reaction was planned to construct the strained and densely functionalized pentacyclic cores of the molecules from acyclic starting materials. After difficulties were encountered in a first-generation synthesis plan toward himeradine A, a second-generation synthesis plan was eventually successful in accomplishing the first total synthesis of fastigiatine via a formal [3+3]-cycloaddition reaction and a retro-aldol tandem transannular Mannich reaction sequence. In part two of this thesis, syntheses of the hibarimicin aglycons, including HMP-Y1, atrop-HMP-Y1, hibarimicinone, atrop-hibarimicinone, and HMP-P1, are reported. These natural products are amongst the largest and most complex type-II polyketides isolated. A novel benzylic fluoride Michael-Claisen reaction sequence was developed to construct the complete carbon skeleton of HMP-Y1 and atrop-HMP-Y1 via a symmetrical bidirectional double annulation reaction. Through efforts to convert HMP-Y1 derivatives to hibarimicinone and HMP-P1, a biomimetic mono-oxidation to desymmetrize protected HMP-Y1 was realized. A bidirectional unsymmetrical double annulation and biomimetic etherification were developed to construct the polycyclic and highly-oxidized skeleton of hibarimicinone, atrop-hibarimicinone, and HMP-P1. Lastly, a pH-dependent rotational barrier about the C2-C2' bond of hibarimicinone was discovered, which provides valuable information for achieving the syntheses of the glycosylated congeners of hibarimicinone. |
| Genre | Thesis |
| Topic | Alkaloids -- Synthesis |
| Identifier | http://hdl.handle.net/1957/53105 |
