Credneramides A and B: Neuromodulatory Phenethylamine and Isopentylamine Derivatives of a Vinyl Chloride-Containing Fatty Acid from cf. Trichodesmium sp. nov.

Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (3), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micromolar concentrations (1, IC 50 4.0 μM; 2, IC 50 3.8 μM).Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (3), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micromolar concentrations (1, IC 50 4.0 μM; 2, IC 50 3.8 μM)

Erratum: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

International Chicken Genome Sequencing Consortium. The Original Article was published on 09 December 2004. Nature432, 695–716 (2004). In Table 5 of this Article, the last four values listed in the ‘Copy number’ column were incorrect. These should be: LTR elements, 30,000; DNA transposons, 20,000; simple repeats, 140,000; and satellites, 4,000. These errors do not affect any of the conclusions in our paper. Additional information. The online version of the original article can be found at 10.1038/nature0315

Organic synthesis as an effective approach to chemical, pharmaceutical, and biosynthetic investigations of natural products

The partnership between natural products and synthetic organic chemistry date back to the origin of organic chemistry itself. While natural products became a major driving force for the development of novel organic reactions and synthetic strategies, organic synthesis has contributed in many ways to the elucidation and confirmation of structure, pharmaceutical development, and biosynthetic studies of natural products. Due to the recent advances in both of these two disciplines, there are new opportunities and issues surrounding natural products that organic synthesis can be applied to, and such studies comprise this dissertation. Chapter I introduces the background information and rationale for the dissertation research, which is based on the history of organic chemistry and newly emerging research topics in natural products chemistry. Chapter II describes the isolation, characterization, and toxicological evaluation of polybrominated diphenyl ethers from a mixed assemblage of a marine red alga and cyanobacteria. Chapter III describes the isolation, characterization, and biological evaluation of a novel vinylchloride-containing fatty acid, credneric acid, from a Lyngbya sp. Chapter IV describes the conception of a method for determining the absolute stereochemistry of natural products lacking proper functional groups for derivatization. This methodology was applied to a cyclopropane-containing fatty acid and resulted in a conflict with newly published literature, which is discussed in detail. Chapter V describes the development of an expedient and efficient total synthesis of a novel alkaloid, epiquinamide, isolated from the skin of a rainforest frog, Epipedobates tricolor. This work contributed to clarifying the identity of a potent and selective nicotinic receptor agonistic activity observed in the extract of E. tricolor. Chapter VI describes the development of a total synthesis of a marine cyanobacterial metabolite, somocystinamide A, which has been shown to be a potent inhibitor of endothelial cell proliferation and angiogenesis. The synthesis was later modified for scalability to meet the need for further pharmaceutical investigations of this important natural product. Chapter VII describes the synthetic investigations on scytonemin, a cyanobacterial metabolite possessing UV-blocking properties. Through this work, many intriguing insights into the biosynthesis of the natural product were obtained. Finally, Chapter VIII provides the conclusions drawn from this dissertation research

Organic synthesis as an effective approach to chemical, pharmaceutical, and biosynthetic investigations of natural products

The partnership between natural products and synthetic organic chemistry date back to the origin of organic chemistry itself. While natural products became a major driving force for the development of novel organic reactions and synthetic strategies, organic synthesis has contributed in many ways to the elucidation and confirmation of structure, pharmaceutical development, and biosynthetic studies of natural products. Due to the recent advances in both of these two disciplines, there are new opportunities and issues surrounding natural products that organic synthesis can be applied to, and such studies comprise this dissertation. Chapter I introduces the background information and rationale for the dissertation research, which is based on the history of organic chemistry and newly emerging research topics in natural products chemistry. Chapter II describes the isolation, characterization, and toxicological evaluation of polybrominated diphenyl ethers from a mixed assemblage of a marine red alga and cyanobacteria. Chapter III describes the isolation, characterization, and biological evaluation of a novel vinylchloride-containing fatty acid, credneric acid, from a Lyngbya sp. Chapter IV describes the conception of a method for determining the absolute stereochemistry of natural products lacking proper functional groups for derivatization. This methodology was applied to a cyclopropane-containing fatty acid and resulted in a conflict with newly published literature, which is discussed in detail. Chapter V describes the development of an expedient and efficient total synthesis of a novel alkaloid, epiquinamide, isolated from the skin of a rainforest frog, Epipedobates tricolor. This work contributed to clarifying the identity of a potent and selective nicotinic receptor agonistic activity observed in the extract of E. tricolor. Chapter VI describes the development of a total synthesis of a marine cyanobacterial metabolite, somocystinamide A, which has been shown to be a potent inhibitor of endothelial cell proliferation and angiogenesis. The synthesis was later modified for scalability to meet the need for further pharmaceutical investigations of this important natural product. Chapter VII describes the synthetic investigations on scytonemin, a cyanobacterial metabolite possessing UV-blocking properties. Through this work, many intriguing insights into the biosynthesis of the natural product were obtained. Finally, Chapter VIII provides the conclusions drawn from this dissertation research

Synthesis and biological evaluation of the [d-MeAla(11)]-epimer of coibamide A.

Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the resin and its subsequent macrolactonization. The peptide sequence of the linear coibamide A precursor was constructed on a solid-support following the optimization of the coupling conditions, where numerous coupling agents were evaluated. The macrocyclization of the resulting linear peptide provided the [d-MeAla(11)]-epimer of coibamide A, which exhibited nanomolar cytotoxic activity towards a number of human cancer cell lines

Credneramides A and B: Neuromodulatory Phenethylamine and Isopentylamine Derivatives of a Vinyl Chloride-Containing Fatty Acid from cf. Trichodesmium sp nov.

Credneramides A (1) and B (2), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. Trichodesmium sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (3), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micro-molar concentrations (1, IC50 4.0 mu M; 2, IC50 3.8 mu M).NIH [NS 053398, ICBG FIC TW006634]NI

Credneramides A and B: Neuromodulatory Phenethylamine and Isopentylamine Derivatives of a Vinyl Chloride-Containing Fatty Acid from cf. <i>Trichodesmium</i> sp. nov.

Credneramides A (<b>1</b>) and B (<b>2</b>), two vinyl chloride-containing metabolites, were isolated from a Papua New Guinea collection of cf. <i>Trichodesmium</i> sp. nov. and expand a recently described class of vinyl chloride-containing natural products. The precursor fatty acid, credneric acid (<b>3</b>), was isolated from both the aqueous and organic fractions of the parent fraction as well as from another geographically and phylogenetically distinct cyanobacterial collection (Panama). Credneramides A and B inhibited spontaneous calcium oscillations in murine cerebrocortical neurons at low micromolar concentrations (<b>1</b>, IC₅₀ 4.0 μM; <b>2</b>, IC₅₀ 3.8 μM)