Browsing by Subject "Gymnodimine"
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Item Studies toward the total synthesis of the marine toxin, (-)-gymnodimine(2009-05-15) Kong, Ke(-)-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.Item Synthesis of Haptens for the Marine Toxin, Gymnodimine; Synthesis of Beta-lactone Fused Carbocycles and Nitrogen Heterocycles; Efforts Toward the Synthesis of the Proposed Structure of Thiolyngbyan(2011-08-08) Lee, Chang SukContamination of seafood by marine toxins has been a consistent public health problem. Gymnodimine (GYM) is a member of a family of spirocyclic imine containing marine natural products which was shown to be highly toxic (LD50 96 mg/kg, intraperitoneal injection); thus ensuring public safety requires stringent monitoring of gymnodimine. Current detection methods for GYM and spirolides include the mouse bioassay and LC-MS-based detection techniques which, however, have significant limitations. Therefore, more efficient and convenient detection methods are required. Building on our recently completed total synthesis of (-)-gymnodimine, the synthesis of two haptens were targeted for eventual production of monoclonal antibodies (mAb) to be used in an eventual Enzyme-Linked Immunosorbent Assay (ELISA) for gymnodimine. As an extension of the intramolecular nucleophilic catalyzed aldol lactonization (NCAL) process from aldehyde acid to keto acid substrates, carbocyclic and nitrogen heterocyclic B-lactones were synthesized. Demonstration of the utility of the NCAL process for keto acids was applied to the synthesis of dihydroplakevulin A and the core of tussilagine. In addition, although initial attempts to develop guanidine catalysts for the asymmetric NCAL process were unsuccessful, homobenzotetramisole (HBTM) was found to be a suitable asymmetric catalyst for keto acid substrates. Finally, synthetic studies toward the proposed structure of thiolyngbyan are described. Thiolyngbyan was isolated from a blue-green algae and it exhibited antifungal activity.