(-)-Gymnodimine is a member of a growing family of spirocylic imine
containing marine natural products. The construction of the complete skeleton of (-)-
gymnodimine has been accomplished in a convergent manner in 23 steps (the longest
linear sequence).
A highly diastereo- and enantioselective Diels-Alder reaction employing
bis(oxazoline)·Cu(II) catalyst provided the spirolactam core structure of gymnodimine
bearing a quaternary carbon stereogenic center. An improved procedure for
hydrostannylation of the hindered internal triple bond in 96a was discovered by slow
addition of tributyltin hydride to minimize formation of hydrogenated byproduct.
Fragment coupling featured a Nozaki-Hiyama-Kishi reaction between a vinyl
iodide derived from the spirolactam and a tetrahydrofuran moiety. The macrocyclization
was realized through a rather unusual intramolecular opening of an activated Ntosyllactam
by an alkyllithium species generated in situ. The butenolide was appended
through a vinylogous Mukaiyama aldol addition of silyloxyfuran 155 to the ketone 163 under meticulously controlled conditions. The generality of this process was explored in
some detail. Addition of silyloxyfurans to cyclohexanones proceeds with moderate to
good diastereoselectivities. The potential application of this process to the synthesis of
butenolide and g-lactone containing natural products was demonstrated by further
transformations of the addition adducts.
Finally, toward our goal of developing an enzyme-linked immunosorbent assay
(ELISA) for gymnodimine monitoring a hapten derived from the tetrahydrofuran has
been synthesized. Even though the raised antibodies failed to recognize the natural
product itself, the results provided some information regarding the essential structural
elements of an efficient hapten.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2447 |
| Date | 15 May 2009 |
| Creators | Kong, Ke |
| Contributors | Romo, Daniel |
| 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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