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Structure and biosynthesis of marine cyanobacterial natural products : development and application of new NMR methods

This thesis is an account of my explorations into the field of natural products
chemistry. These investigations led to the discovery of several novel secondary
metabolites isolated from the marine cyanobacterium Lyngbya majuscula. In addition,
biosynthetic investigations were undertaken using stable isotope-labeled precursors.
The dominant role that NMR spectroscopy plays in the field of natural products
chemistry has led to the development of several novel pulse sequences.
Hectochlorin was discovered during a phytochemical investigation of a
cultured L. majuscula originally collected off the coast of the Caribbean Island,
Jamaica. The absolute stereochemistry was determined by X-ray crystallography.
Through a series of biological evaluations, this compound was found to stimulate actin
The jamaicamide class of compound was isolated from the same organism that
yielded hectochlorin. The structures were elucidated utilizing a variety of NMR
methods, including a newly developed pulse sequence. Because the producing
organism was in culture, a biosynthetic pathway investigation ensued to elucidate the
carbon framework in jamaicamide A.
The marine natural product barbamide is intriguing due to the incorporation of
a trichloromethyl group into its molecular constitution. Further investigation into the
timing of the chlorination reaction has been pursued. In addition, the isolation of
dechlorobarbamide and the determination of the absolute stereochemistry assignment
of barbamide was accomplished.
A reevaluation of the stereochemistry of antillatoxin necessitated a correction
in the original assignment. Four antillatoxin stereoisomers were obtained from a
collaborator and found to possess differing levels of biological activity. The three
dimensional solution structures of these isomers were evaluated in an effort to
understand the role these stereochemical features play in the observed bioactivity. The
structures were determined utilizing NMR-derived constraints applied to molecular
modeling calculations.
The development of two new pulse sequences for the determination of long-range
heteronuclear coupling constants was also accomplished. The 1,1 ADEQUATE
experiment was modified to yield an ACCORDIAN experiment which can be
optimized to observe of a wide range of ��J[subscript cc] couplings. This new experiment is
demonstrated for a model compound as well as for the new marine natural product
jamaicamide A. / Graduation date: 2002
Date29 June 2001
CreatorsMarquez, Brian L.
ContributorsGerwick, William H.
Source SetsOregon State University
Detected LanguageEnglish

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