Apoptolidin 1.1 was isolated in 1997 by Hayakawa and co-workers from a soil
bacterium Nocardiopsis sp. during screening for specific apoptosis inducers. The
primary biological test revealed that this polyketide macrolide induced apoptosis in cells
transformed with the adenovirus type E1A oncognene, but not normal cells. This
dissertation describes the latest studies in understanding of apoptolidin’s biological
activity mechanism and previous contributions towards its total synthesis. Synthesizing
apoptolidinone 1.26 by an intra-molecular Horner-Wadsworth-Emmons approach
featuring a Suzuki coupling, cross metathesis and two diastereoselective aldol reactions is
discussed. 15 mg apoptolidinone is prepared via our previously developed intramolecular
Suzuking coupling approach.
Ammocidin 3.1, which was found to induce apoptosis in Ba/F3-v12 cells in an IL-
3 free medium, is a specific apoptosis inducer discovered by Hayakawa and co-workers
in 2001 from Saccharothrix sp. AJ9571. A strategy featuring Suzuki coupling, cross
metathesis, Yamaguchi macrolactonization and three asymmetric aldol reactions was
applied to the total synthesis of ammocidinone 3.6, the aglycone of ammocidin. The
preparation of the key building blocks was discussed in the following chapter: aldehyde
3.8 (C14-C19) was synthesized via Sharpless asymmetric epoxidation; ethyl ketone 3.9’ (C20-C28) was prepared via Kobayashi and Crimmins’s asymmetric aldol
methodologies; aldehyde 3.14 (C7-C13) was generated by Brown crotylation and cross
metathesis.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-1054 |
| Date | 15 May 2009 |
| Creators | Liu, Qingsong |
| Contributors | Sulikowski, Gary A. |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | electronic, application/pdf, born digital |
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