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- Title
- Therapeutic potential, mechanism of action, and ecology of novel marine natural products.
- Creator
- Winder, Priscilla L., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The projects described in this dissertation are focused on compounds derived from the marine environment. Chapter 1 gives an introduction to the study of marine natural products to treat human ailments and a thorough review on compounds from lithistid sponges that have been isolated or synthesized since 2000. Chapter 2 describes the isolation and structure elucidation of two sesquiterpene substituted benzoquinone derivatives, petrosiquinones A and B, from a deep-water marine sponge from the...
Show moreThe projects described in this dissertation are focused on compounds derived from the marine environment. Chapter 1 gives an introduction to the study of marine natural products to treat human ailments and a thorough review on compounds from lithistid sponges that have been isolated or synthesized since 2000. Chapter 2 describes the isolation and structure elucidation of two sesquiterpene substituted benzoquinone derivatives, petrosiquinones A and B, from a deep-water marine sponge from the Family Petrosiidae. Although initially purified following activity in a (Sb(B-catenin/Tcf4 assay they were later followed using tumor cell line cytotoxicity assays. Petrosiquinone A was the more active of the two compounds with moderate cytotoxicity in the DLD-1, PANC-1, and AsPC-1 cell lines. In Chapter 3, the isolation and structure elucidation of two new marine-derived macrolides, madeirolide A and B, isolated from a deep-water lithistid sponge of the genus Leiodermatium is described., They were isolated using numerous chromatographic techniques and the structures were elucidated on the basis of 1D and 2D NMR spectra coupled with high resolution-mass spectrometry (HR-MS) data. Madeirolide A and B inhibited the growth of the fungal pathogen Candida albicans with minimum inhibitory concentrations (MIC) of 12.5 and 25 (So(Bg/mL, respectively, but were not cytotoxic in tumor cell assays under the conditions tested. Chapter 4 describes work performed to determine the molecular target of lasonolide A using affinity chromatography. The target of lasonolide A is of interest since lasonolide A is known to kill cancer cells in vitro through a unique mechanism., This chapter highlights the research performed to create an affinity matrix with immobilized lasonolide. A target has not been confirmed but there are a number of interesting hits that are being pursued. In Chapter 5, a liquid chromatography-mass spectrometry (LC-MS) screening method was established in order to rapidly identify the metabolites from numerous collections of Lyngbya spp. obtained from Broward and Lee County, Florida sites that may help marine ecologists assess the effects of Lyngbya spp. blooms on the environment. A link between the metabolites produced and nutrients from both the algal tissue and water column was also explored.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/369392
- Subject Headings
- Natural products, Therapeutic use, Sponges, Ecology, Marine resources, Research, Marine biotechnology
- Format
- Document (PDF)
- Title
- The chemistry of Briareum asbestinum.
- Creator
- Rondeau, Melody D., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Briareum asbestinum, a soft coral, is a rich source of diterpenoid natural products. The secondary metabolites of B. asbestinum fall into four classes : asbestinins, briarellins, briareolate esters, and briaranes. Briareolate esters have been shown to possess biological activity and were previously only reported from Tobago. Our group recently isolated briareolate esters from a specimen collected off the coast of Boca Raton, Florida. To determine whether location has an impact on the...
Show moreBriareum asbestinum, a soft coral, is a rich source of diterpenoid natural products. The secondary metabolites of B. asbestinum fall into four classes : asbestinins, briarellins, briareolate esters, and briaranes. Briareolate esters have been shown to possess biological activity and were previously only reported from Tobago. Our group recently isolated briareolate esters from a specimen collected off the coast of Boca Raton, Florida. To determine whether location has an impact on the chemistry produced by the organism, a method to discern between chemotypes was sought. Several techniques including thin layer chromatography (TLC), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and sclerite analysis were employed, with NMR being the most successful method. By utilizing both 1H and COSY NMR experiments, it is possible to differentiate between the chemotypes of B. asbestinum. Application of this method allowed analysis of chemical variability with respect to location.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3355882
- Subject Headings
- Heterocyclic compounds, Synthesis, Coral reef ecology, Marine organisms, Environmental aspects, Biochemical markers
- Format
- Document (PDF)
- Title
- An extraction optimization and determination of the absolute configuartion of clathric acid.
- Creator
- Rueda de Leon, Rolando, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Current research in natural products has heavily focused on the identification of potent biologically active compounds, specifically for drug development. The project detailed in this thesis focuses on the extraction of compounds from marine invertebrates as well as defining the absolute configuration for a compound. Utilizing marine invertebrates, the sonications method developed in this thesis provides an alternative approach to rapidly extract compounds for primary screening. This method...
Show moreCurrent research in natural products has heavily focused on the identification of potent biologically active compounds, specifically for drug development. The project detailed in this thesis focuses on the extraction of compounds from marine invertebrates as well as defining the absolute configuration for a compound. Utilizing marine invertebrates, the sonications method developed in this thesis provides an alternative approach to rapidly extract compounds for primary screening. This method is viable compared to a traditional overnight extraction method, without suffering compound degredation... Previously, clathric acid was isolated from an unknown Clathria sp. This compound is a bibyblic C-21 terpenoid shown to have mild antimicrobial activity against gram positive bacteria. With only its relative configuration established, additional amounts of clathric acid were required to define the overall absolute configuration. Identifying the Clathria sp. to be Clathria compressa, through spicule analysis, additional sponge tissues were then collected off the coast of Boca Raton, Florida to isolate additional quatities of clathric acid. The absolulte configuration was determined through circular dichroism and the octant rule to establish a final configuration for clathric acid's four carbon stereocenters to be: (3S, 7S, 8R, and 12S).
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3355874
- Subject Headings
- Organic compounds, Analysis, Extraction (Chemistry), Natural products, Therapeutic use, Marine biotechology, Marine resources, Research, Sponges, Ecology
- Format
- Document (PDF)
- Title
- An ecological study of photoautotrophs in Lake Worth.
- Creator
- Bolter, Keren P., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Little Lake Worth (LLW) (800 m x 200 m x 8« m) is an artificially deep, monomictic marine basin. Pigments and other water quality parameters (O2, pH, T, S, NO3 -. etc.) were utilized to characterize phototrophic communities and water quality. The water column is dominated by diatoms except in the hypolimnon during stratification events (late Summer) when strong anoxia and H2S favors abundant Chlorobium sulfur bacteria. Results indicate nitrate-enriched freshwater baseflow indicative of septic...
Show moreLittle Lake Worth (LLW) (800 m x 200 m x 8« m) is an artificially deep, monomictic marine basin. Pigments and other water quality parameters (O2, pH, T, S, NO3 -. etc.) were utilized to characterize phototrophic communities and water quality. The water column is dominated by diatoms except in the hypolimnon during stratification events (late Summer) when strong anoxia and H2S favors abundant Chlorobium sulfur bacteria. Results indicate nitrate-enriched freshwater baseflow indicative of septic tank seepage during the wet season. This also appears to lead to the accumulation of concentrated organic matter in the sediment. LLW is a potential threat to the health of the ecosystem and the humans using it recreationally. More research is required to verify the effectiveness of restoration options. The spatial and temporal distribution of Chlorobium (phaeovibiroides tent.) and their Bacteriochlorophyll-e homologues is described and compared to similar studies.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/3151675
- Subject Headings
- Algae culture, Water quality, Biotic communities, Marine sediments
- Format
- Document (PDF)
- Title
- 9,11-secogorgosterol biosynthesis in gorgonians.
- Creator
- Kellman, Jaelle, Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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9,11-secogorgosterol is a secondary metabolite from the gorgonian Pseudopterogorgia americana which acts as a chemical defense. The soft coral lives in a symbiotic association with unicellular algae known as zooxanthellae. A biosynthetic investigation, using in vivo and in vitro methods, has resulted in the identification of the metabolic precursor of 9,11-secogorgosterol as gorgosterol. This finding is significant as it indicates that the conversion of gorgosterol to 9,11-secogorgosterol is...
Show more9,11-secogorgosterol is a secondary metabolite from the gorgonian Pseudopterogorgia americana which acts as a chemical defense. The soft coral lives in a symbiotic association with unicellular algae known as zooxanthellae. A biosynthetic investigation, using in vivo and in vitro methods, has resulted in the identification of the metabolic precursor of 9,11-secogorgosterol as gorgosterol. This finding is significant as it indicates that the conversion of gorgosterol to 9,11-secogorgosterol is due to gorgonian metabolism. Since gorgosterol is known to be a product of zooxanthellae metabolism, this would be the first example of a defensive secondary metabolite being produced by two organisms living in symbiosis. A viable acetone powder has been generated from the crude cell-free extract and has demonstrated the efficient transformation of gorgosterol to 9, 11-secogorgosterol. This indicates possible future value as a synthetic tool for secosterol production.
Show less - Date Issued
- 1995
- PURL
- http://purl.flvc.org/fcla/dt/15180
- Subject Headings
- Sterols--Synthesis, Alcyonacea
- Format
- Document (PDF)
- Title
- ATOMIC MOLECULAR THEORY: A PROGRAMMED TEXT USED IN THE TEACHING OF BASIC ATOMIC AND MOLECULAR ORBITAL THEORY IN A HIGH SCHOOL PROGRAM OF CHEMISTRY.
- Creator
- SEVERANCE, H. WILSON, JR., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
This program was developed from necessity found in the teaching of molecular geometry to high school chemistry classes. Recent journals and textbooks were consulted in evaluation of the modern emphasis on instruction in molecular geometry at the high school level, and the topic was then developed fully for use in the chemistry course at the Ransom School, serving as a base for other instructional units. A self-teaching concept was employed in this manual in order that the student might...
Show moreThis program was developed from necessity found in the teaching of molecular geometry to high school chemistry classes. Recent journals and textbooks were consulted in evaluation of the modern emphasis on instruction in molecular geometry at the high school level, and the topic was then developed fully for use in the chemistry course at the Ransom School, serving as a base for other instructional units. A self-teaching concept was employed in this manual in order that the student might proceed at his own pace and according to his own needs. The principal intention was to familiarize the student with the shapes and configurations of various molecules and thereby to give him greater insight into the physical picture of molecular interaction in chemical reaction.
Show less - Date Issued
- 1974
- PURL
- http://purl.flvc.org/fcla/dt/13656
- Subject Headings
- Molecular orbitals--Study and teaching (Secondary), Chemistry--Study and teaching (Secondary)--Programmed instruction, Atomic theory--Study and teaching (Secondary)
- Format
- Document (PDF)
- Title
- Initial investigations of the magnetic circular dichroism of isobutene using synchrotron radiation in the vacuum ultraviolet region.
- Creator
- Sanders, Clifford., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Ethylene is the simplest alkene. The carbon-carbon double bond is ubiquitous in the field of chemistry. Ethylene serves as the basis for understanding these molecules. Thus, the assignment of the electronic transitions in ethylene is an important endeavor that many scientists have undertaken, but are yet to decipher theoretically or experimentally. Synchrotron Radiation in the vacuum ultraviolet region allows for magnetic circular dichroism (MCD) measurements of ethylene and other simple...
Show moreEthylene is the simplest alkene. The carbon-carbon double bond is ubiquitous in the field of chemistry. Ethylene serves as the basis for understanding these molecules. Thus, the assignment of the electronic transitions in ethylene is an important endeavor that many scientists have undertaken, but are yet to decipher theoretically or experimentally. Synchrotron Radiation in the vacuum ultraviolet region allows for magnetic circular dichroism (MCD) measurements of ethylene and other simple alkenes. Studies of ethylene and propylene revealed that the páap* (AgáaB1u ethylene notation) transition is not the lowest energy transition. The páa3s(R) (AgáaB3u ethylene notation) is the lowest energy transition. To further this investigation, MCD and absorption measurement were carried out on isobutene. The isobutene spectra clearly showed four electronic transitions in the 156 to 212 nm wavelength region. These four isobutene transitions have been assigned as páa3s, páap*, páa3p(Sv (Band páa3px proceeding from lower energy to higher energy. The present results support the assignments in ethylene and propylene.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/228772
- Subject Headings
- Bioactive compounds, Testing, Magnetic circular dichroism, Molecular spectroscopy, Spectrum analysis, Quantum theory
- Format
- Document (PDF)
- Title
- Isolation and characterization of novel conopeptides from the marine cone snail: Conus brunneus.
- Creator
- Pflueger, Fred C., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Cone snails are predatory marine gastropods that use venom for means of predation and defense. This venom is a complex mixture of conopeptides that selectivity binds to ion channels and receptors, giving them a wide range of potential pharmaceutical applications. Conus brunneus is a wide spread Eastern Pacific cone snail species that preys upon worms (vermivorous). Vermivorous cone snails have developed very specific biochemical strategies for the immobilization of their prey and their venom...
Show moreCone snails are predatory marine gastropods that use venom for means of predation and defense. This venom is a complex mixture of conopeptides that selectivity binds to ion channels and receptors, giving them a wide range of potential pharmaceutical applications. Conus brunneus is a wide spread Eastern Pacific cone snail species that preys upon worms (vermivorous). Vermivorous cone snails have developed very specific biochemical strategies for the immobilization of their prey and their venom has not been extensively studied to date. The main objective of this dissertation is the characterization of novel conopeptides isolated from Conus brunneus. Chapter 1 is an introduction and background on cone snails and conopeptides. Chapter 2 details the isolation and characterization of a novel P-superfamily conotoxin. Chapter 3 presents the 3D solution structure of the novel P-superfamily conotoxin. Chapter 4 details the isolation and characterization of two novel M-superfamily conotoxins. Chapter 5 covers the use of nano-NMR to characterize a novel P-superfamily conotoxin using nanomole quantities of sample. Chapter 6 is a reprint of a paper published in the Journal of the American Chemical Society in which we combined and implemented techniques developed in the previous chapters to report the presence of D-(Sd(B-Hydroxyvaline in a polypeptide chain. This dissertation contains the first reported work of a P-superfamily structure obtained directly from the crude venom therefore accurately representing native post-translational modifications. In this paper, crude cone snail venom was characterized by: high performance liquid chromatography, nuclear magnetic resonance spectroscopy, nanonuclear magnetic resonance spectroscopy, mass spectrometry, amino acid analysis, Edman degradation sequencing, and preliminary bioassays.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/FAU/3337185
- Subject Headings
- Gastropoda, Venom, Peptides, Structure, Conus, Venom
- Format
- Document (PDF)
- Title
- Isolation and structure elucidation of new compounds from Cornus Controversa and Delphinium Chrysotrichum.
- Creator
- He, Yangqing, West, Lyndon, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The aim of this dissertation was to explore structurally unique secondary metabolites from herb medicinal plants Cornus controversa and Delphinium chrysotrichum. The introduction in the first chapter provides a detailed review about the research progress of chemical constitutents of the genus Cornus. In addition, its pharmacological activities were also summarized in this chapter to provide a framework for understanding the roles of medicinal herbs belong to genus Cornus as anti-diabetes...
Show moreThe aim of this dissertation was to explore structurally unique secondary metabolites from herb medicinal plants Cornus controversa and Delphinium chrysotrichum. The introduction in the first chapter provides a detailed review about the research progress of chemical constitutents of the genus Cornus. In addition, its pharmacological activities were also summarized in this chapter to provide a framework for understanding the roles of medicinal herbs belong to genus Cornus as anti-diabetes therapeutics and to deliver useful information for further research. In chapter two, seven new compounds, including one iridoid glucoside, cornoside A (59), five iridoid aglycones, cornolactones A – E (60 – 64) and one indenone glucoside, cornoside B (65), together with 10 known compounds have been isolated from the leaves of Cornus controversa. The structures of these compounds were established by interpretation of spectroscopic data. Cornolactone A (61) is the first natural cis-fused tricyclic dilactone iridoid containing both a five- and six-membered lactone ring. Cornoside B (65) is the first alkaloid isolated from the genus Cornus bearing an indole-3-lactic acid-11--D-glucopyranoside skeleton. In chapter three, we described the structure elucidation of three new diterpenoid alkaloids delphatisine D (77), chrysotrichumines A (78) and B (79), as well as 11 known compounds from the whole plants of Delphinium chrysotrichum. Delphatisine D (77) is a rare atisine-type alkaloid from genus Delphinium and is the C-15 epimer of spiramine C which bears an internal carbinolamine ether linkage (NCOC) between C-7 and C-20. Chrysotrichumine A (78) is a rare natural C19-diterpenoid alkaloid possessing a nitrone group between C-17 and C-19. In addition, their cytotoxic activity against human breast cancer cell lines of MCF-7 and MDA-MB-231 were also reported. In chapter four, the detailed extraction and isolation procedures of the new compounds, cornosides A and B, cornolactones A – E, delphatisine D, chrysotrichumine A and B, as well as of all the known compounds were described. In addition, the experimental procedures for the determination of PPARγ and LXR agonistic activities and the MTT cytotoxicity assay were listed in this chapter.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00004121
- Subject Headings
- Medicinal plants., Delphinium., Cornus (Plants)
- Format
- Document (PDF)
- Title
- Isolation and Structural Elucidation of Novel Bioactive Natural Products from Marine Organisms of the Western Atlantic Ocean.
- Creator
- Zhang, Long, West, Lyndon, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The aim of this dissertation was to elaborate the exploration of biologically active secondary metabolites from the marine sponge Cacospongia cf. linteiformis collected from the Bahamas and the soft coral Briareum asbestinum collected from two different sites in Florida State, Boca Raton and Dry Tortugas. In chapter one, a review on previous chemical and biological studies of the marine sponge C. cf. linteiformis and soft coral B. asbestinum is provided. Particular attention is given to...
Show moreThe aim of this dissertation was to elaborate the exploration of biologically active secondary metabolites from the marine sponge Cacospongia cf. linteiformis collected from the Bahamas and the soft coral Briareum asbestinum collected from two different sites in Florida State, Boca Raton and Dry Tortugas. In chapter one, a review on previous chemical and biological studies of the marine sponge C. cf. linteiformis and soft coral B. asbestinum is provided. Particular attention is given to spongianolides and briarellins, two important classes of compounds isolated from C. cf. linteiformis and B. asbestinum, respectively, and their structural features and diverse bioactivities. In chapter two, the isolation and relative configuration determination of four epimeric sesterterpenoids, spongianolides E & F (18c, 18d, 19c, 19d) from C. cf. linteiformis collected from the Bahamas are discussed. Thanks to chemical modification (acetylation), diastereomeric 18c&18d and 19c&19d, respectively, were able to be isolated using chromatographic techniques for the first time, and then the relative configurations of 18c, 18d, 19c, 19d were determined based on NOESY NMR experiments. The bioactivity of mixture of compounds 18c, 18d, 19c, 19d were tested and it exhibited inhibition against Schnurri-3 (a regulator of postnatal bone mass). In chapter three, the isolation and structural elucidation of four new compounds, florellins A-D (49-52), from B. asbestinum collected off the coast of Boca Raton, FL are discussed. The molecular structures of these compounds were established by spectroscopic analysis. Compounds 49-52 are the first briarellins containing an acyl group at C-13, while 49 and 50 are the first briarellins possessing acylation at C-15. Florellins A–C (49-51) were screened and found cytotoxic against three human cell lines, BT474, WM266−4 and HEK293. In chapter four, the isolation and structural elucidation of four new compounds, florellins E-H (57-60), from B. asbestinum collected in Dry Tortugas, FL are discussed. The molecular structures of these compounds were established by spectroscopic analysis. Florellins F (58) and H (60) were screened against three human cell lines, BT474, WM266−4 and HEK293, but no cytotoxicity was exhibited. In chapter five, all the experimental procedures are described, including analytical instruments, animal materials, extraction and isolation processes, spectroscopic data and protocols of bioassays.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004850, http://purl.flvc.org/fau/fd/FA00004850
- Subject Headings
- Pharmacognosy., Natural products--Analysis., Marine pharmacology., Marine biotechnology., Marine algae--Biotechnology., Bioactive compounds.
- Format
- Document (PDF)
- Title
- Isocation and characterization of conotoxins from the venom of Conus Planorbis and Conus Ferrugineus.
- Creator
- Pak, Adriana, Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The venom of marine gastropods belonging to the genus Conus has yielded numerous structurally and functionally diverse peptidic components. The increase variety of bioactive peptides identified in cone snail venoms is the product of the variety of molecular adaptations taken by Conus species in evolving neuroactive molecules to suit their diverse biological purposes. Toxins from cone snails are classified into two major groups. One group consists of disulfide-rich peptides commonly termed...
Show moreThe venom of marine gastropods belonging to the genus Conus has yielded numerous structurally and functionally diverse peptidic components. The increase variety of bioactive peptides identified in cone snail venoms is the product of the variety of molecular adaptations taken by Conus species in evolving neuroactive molecules to suit their diverse biological purposes. Toxins from cone snails are classified into two major groups. One group consists of disulfide-rich peptides commonly termed conotoxins; the second group comprises peptides with only one disulfide bond or none. In this work, we present the discovery and characterization from the marine snails C. planorbis and C. ferrugineus. Both species are commonly found in the Indo-Pacific region and are very similar and is not distinguishable by size and shape of the shell. Novel P and T-Supefamiles were found in both species along with small linear peptides with have a high frequency of tyrosine residues. Each chapter contains a detailed look at the discovery process for the isolation and characterization of C. planorbis and C. ferrugineus. At discussion part, we also compared the peptides isolated in this work with other peptides from the literature.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00004146, http://purl.flvc.org/fau/fd/FA00004146
- Subject Headings
- Conus, Gastropoda -- Venom, Peptides -- Structure, Venum
- Format
- Document (PDF)
- Title
- Isolation and Semi-synthesis of Marine Diterpenoids.
- Creator
- Scesa, Paul D., West, Lyndon, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Natural products play a historical role in the discovery of medicine but present unique challenges for chemical isolation, identification and production. In this work we describe the identification of twenty novel diterpenoids. These were isolated by use of chromatography, and the structures determined by spectroscopic methods, primarily 1D and 2D NMR. Six of these possess unprecedented diterpenoid skeletons and two of them show significant growth inhibitory effects on cancer cell lines in...
Show moreNatural products play a historical role in the discovery of medicine but present unique challenges for chemical isolation, identification and production. In this work we describe the identification of twenty novel diterpenoids. These were isolated by use of chromatography, and the structures determined by spectroscopic methods, primarily 1D and 2D NMR. Six of these possess unprecedented diterpenoid skeletons and two of them show significant growth inhibitory effects on cancer cell lines in vitro (GI50 < 10 μM). The biomimetic semisynthesis of diterpendoids and analogues is also presented. Access to the bielschowskyane carbon skeleton by dearomatization of a furanocembranoid precursor is described. Highlights include a stereoselective alkene epoxidation, a novel kinetic furan dearomatization method, and an efficient [2+2] photochemical cycloaddition. The role of conformational steering was studied spectroscopically using VT 1H-NMR and NOESY as well as quantum chemical calculations at the DFT level of theory. We also disclose a biomimetic synthesis of providencin using a photochemical Norrish-Yang cyclization. This provided the absolute configuration by chemical correlation with the precursor bipinnatin E, the latter determined by x-ray diffraction. An unexpected, regioisomeric byproduct was observed and a possible mechanism is proposed. A biomimetic synthesis of the diterpene alkaloid aceropterine is also described, using an epoxidation-rearrangement cascade. This work led to a revised structure of aceropterine, formulated by spectroscopic methods. Finally, the isolation and structure elucidation of a novel, cyclic lipopeptide from Pseudomonas sp. is described. The compound was obtained using a unique antibiotic crowd sourcing approach and the structure determined by spectroscopic methods and advanced Marfey’s analysis.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013539
- Subject Headings
- Marine natural products, Diterpenoids, Biomimetics
- Format
- Document (PDF)
- Title
- Isolation and structure elucidation of novel compounds from marine cyanobacteria.
- Creator
- Meickle, Theresa, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The work of this dissertation examined the secondary metabolites of several blooms of the marine cyanobacterium Lyngbya collected in Guam and Florida with an emphasis on the isolation and structure elucidation of novel biologically active compounds. The introduction in Chapter One provides a brief history of marine natural products, a description of cyanobacteria and a summary of peptides isolated from Lyngbya collected in the Caribbean. In Chapter Two, a bioassay-guided fractionation of a...
Show moreThe work of this dissertation examined the secondary metabolites of several blooms of the marine cyanobacterium Lyngbya collected in Guam and Florida with an emphasis on the isolation and structure elucidation of novel biologically active compounds. The introduction in Chapter One provides a brief history of marine natural products, a description of cyanobacteria and a summary of peptides isolated from Lyngbya collected in the Caribbean. In Chapter Two, a bioassay-guided fractionation of a Floridian collection of Lyngbya polychroa led to the isolation and structural determination of the cytotoxin desacetylmicrocolin B and the known compounds microcolins A and B. The structures were established by nuclear magnetic resonance (NMR) spectroscopic analysis. All three compounds inhibited the growth of cancer cell lines HT-29 and IMR-32 at nanomolar concentrations. Microcolins A and B were found to have little activity in the ecological assay against the marine fungus Dendryphiella salina. Chapter Three describes the isolation and structure elucidation of the glycosidic, acyl proline derivative tumonoic acid J from a sample Lyngbya sp. collected in Guam. The planar structure was determined by 1D and 2D NMR spectroscopy in conjunction with high resolution-mass spectrometry (HR-MS) data. Tumonoic acid J showed moderate activity in the ecological assay against the marine fungus D. salina. In Chapter Four, NMR-guided fractionation of a Floridian sample of Lyngbya majuscula led to the isolation of two novel cyclic peptides porpoisamides A and B. The planar structures were determined by 1D and 2D NMR spectroscopy with HR-MS data. The absolute configurations of these two compounds were defined through chiral chromatographic methods and derivatization techniques., The porpoisamides showed only moderate activity in cytotoxicity assays against cancer cell lines HCT-116 and U2OS. Finally, Chapter Five examines a potential ecological role of compounds isolated from marine cyanobacte ria. These secondary metabolites may function as chemical defenses against competing microorganisms within marine environments. Compounds isolated from cyanobacteria were tested for anti-fungal activity against the saprophytic marine fungus D. salina. Three of the six compounds tested produced inhibitory activity at or below their natural concentration.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/2978991
- Subject Headings
- Sponges, Ecology, Cyanobacteria, Biological control, Aquatic ecology
- Format
- Document (PDF)
- Title
- Isolation of briareolate esters from Briareum asbestinum.
- Creator
- Meginley, Rian J., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The gorgonian Briareum asbestinum is widely studied because it possesses highly oxygenated novel structures, many of which exhibit useful biological activities. Recently, two new briarane diterpenoids, briareolate esters J and K, together with two known briareolate esters have been isolated from a specimen of Briareum asbestinum collected off the coast of Boca Raton, Florida. The method used was a 96-well plate real-time cell electronic sensing (RT-CES) system to discover compounds that...
Show moreThe gorgonian Briareum asbestinum is widely studied because it possesses highly oxygenated novel structures, many of which exhibit useful biological activities. Recently, two new briarane diterpenoids, briareolate esters J and K, together with two known briareolate esters have been isolated from a specimen of Briareum asbestinum collected off the coast of Boca Raton, Florida. The method used was a 96-well plate real-time cell electronic sensing (RT-CES) system to discover compounds that impact human embryonic stem cell growth. The compounds were isolated using reversed phase polystyrene divinylbenzene chromatographic support HP20ss followed by normal phased HPLC using a luna silica column. The structures of the compounds were established though the interpretation of spectroscopic data. Activity testing was conducted against hESCs (BG02) with briareolate ester J showing no inhibition activity and briareolate ester K showing mild activity with an EC50 value of 25 (So(BM. These results confirm that the exact confirmation and existence of the (E,Z)-dienone is related to the activity that was observed with the previously isolated briareolate esters L and M.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3360959
- Subject Headings
- Coral reef ecology, Marine organisms, Environmental aspects, Marine natural products, Bioactive compounds
- Format
- Document (PDF)
- Title
- Synthesis, structural characterization and biological studies of organotin polyethers (Sn-O).
- Creator
- Barot, Girish Vallabhbhai., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Cancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin...
Show moreCancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin polyethers (Sn-O) which can be used to combat cancer. Preliminary results from our laboratory using organotin polyethers, that were synthesized by varying the structure of diols showed growth inhibition in Balb-3T3 cells. This study directly led us to hypothesize the two structural windows, first by changing the distance between diol and second, by presence of unsaturation in diols, the biological activity of organotin polyethers (Sn-O) can be enhanced significantly. Different series of polymeric compounds were synthesized based upon these two structural windows and the formation of products was validated using standard techniques like infrared spectroscopy (IR), light scattering photometer, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and nuclear magnetic resonance (NMR). The synthesized polymers arrested the growth of cancer cell lines including bone, prostate, colon, breast, pancreas and lung cancer derived cell lines in vitro. In number of instances where chemotherapeutic index values of two and greater were found that these polymers are significantly more active against cancer cells than non-cancerous cells in culture., These results support the starting premise that the polymers may exhibit cancer cell selectivity. In general, it was found that the presence of unsaturation increased the probability that the polyether would inhibit the growth of various cancer cell lines. Further, in some cases, polyethers with short distances between the oxygen atoms showed a superior ability to inhibit the growth of various cancer cell lines in comparison to those with longer distances between the oxygen atoms. These results provide a framework for the discovery of novel cancer therapeutics.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/186672
- Subject Headings
- Organometallic polymers, Cancer, Molecular aspects, Apoptosis, Molecular aspects, Antineoplastic agents, Testing, Polymers in medicine
- Format
- Document (PDF)
- Title
- Synthesis and new reactions of allenyl carbonyls: studies towards the total synthesis of anti-thrombotic natural products Vitisinol D and C.
- Creator
- Maity, Pradip., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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We report here the development of new and more general synthetic pathways for the preparation of allenyl and alkynyl carbonyls. These highly dense functionalized compounds were utilized as key intermediates for the synthesis of [3.2.1] and [3.3.1] bicyclic framework, the motifs found in many natural products. A convenient method described for the dehydration of ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method...
Show moreWe report here the development of new and more general synthetic pathways for the preparation of allenyl and alkynyl carbonyls. These highly dense functionalized compounds were utilized as key intermediates for the synthesis of [3.2.1] and [3.3.1] bicyclic framework, the motifs found in many natural products. A convenient method described for the dehydration of ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method involves the formation of a vinyl triflate monoanion intermediate that leads to the selective formation of alkynes or allenes depending on additives and conditions used. Product outcomes appear to be a function of unique monoand dianion mechanisms which are described. Our design of a Morita-Baylis-Hilman (MBH) reaction to include a fast silyl 1,3- Brook rearrangement has enabled the first ever anion-catalysis. This new reaction makes possible the addition of both aliphatic and aromatic aldehydes to s ilylallenes leading to carbinol allenoates. These new MBH reactions products allow for a fasttracked synthesis of [3.2.1] bisoxa-bicycles which make up the framework of many biologically active natural products including Vitisinol D. The development of cyclic addition of hydrazine nitrogen to unactivated alkynes catalyzed by non-metals is reported. Starting from readily accessible silyl allenyl esters, alkynyl hydrazines are prepared in one step and subsequently undergo unprecedented cyclization reactions in the presence of ammonium and phosphonium catalysts leading to dehydro-azaproline products. These heterocycles were also produced in high enantiomeric excesses using chiral ammonium phase transfer catalysts via a kinetic resolution pathway., The racemic synthesis of fully functionalized bicyclic core of Vitisinol D was achieved using allenyl ester as a key intermediate. The required electron withdrawing group (EWG) at the position was screened for better addition followed by the compatibility towards successive transformation and, finally, the ease of removal. A reductive aldol method to transform lactone-enol to the desired [3.2.1] bicycle was extensively studied to understand the stereoelectronic requirements for the formation of such bicyclic structures. Due to the necessity of selective protection and deprotection of many phenolic and aliphatic hydroxyls as well as ester groups, orthogonal protecting groups were established accordingly.
Show less - Date Issued
- 2011
- PURL
- http://purl.flvc.org/FAU/3332717
- Subject Headings
- Organic compounds, Synthesis, Carbonyl compounds, Synthesis, Cardiovascular system, Diseases, Treatment
- Format
- Document (PDF)
- Title
- Synthesis and Bioactivity Investigation of Bridged Bicyclic Compounds and a Mechanistic Investigation of a Propargyl Hydrazine Cycloaddition Catalyzed by an Ammonium Salt.
- Creator
- St.Germain, Elijah, Lepore, Salvatore D., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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We report the development of a general route to the synthesis of [4.3.1], [3.3.1], an especially [3.2.1] bicyclic compounds structurally related to vitisinol D, a natural product. This allows for diastereoselective synthesis of bicyclic compounds with five adjacent chiral centers. This route was employed in a preliminary SAR investigation into the neuroprotectant effect of small molecules in an in vivo experiment measuring the degree of restorative effect of synaptic transmission in the...
Show moreWe report the development of a general route to the synthesis of [4.3.1], [3.3.1], an especially [3.2.1] bicyclic compounds structurally related to vitisinol D, a natural product. This allows for diastereoselective synthesis of bicyclic compounds with five adjacent chiral centers. This route was employed in a preliminary SAR investigation into the neuroprotectant effect of small molecules in an in vivo experiment measuring the degree of restorative effect of synaptic transmission in the neuromuscular junction of Drosophila melanogaster larvae under acute oxidative stress. One of the compounds exhibited intriguing potential as a neuroprotectant and outperformed resveratrol in restoring synaptic function under oxidative stress. The hypothesis that bridged bicyclic compounds may hold promise as drug scaffolds due to their conformational rigidity and ability to orient functional appendages in unique orientations is developed. The second focus is a mechanistic investigation into a tetrabutylammoniumcatalyzed cycloaddition as evidence of a novel ammonium-alkyne interaction. A carbamate nitrogen adds to a non-conjugated carbon–carbon triple bond under the action of an ammonium catalyst leading to a cyclic product. Studies in homogeneous systems suggest that the ammonium agent facilitates cyclitive nitrogen–carbon bond formation through a cation–π interaction with the alkyne unit. Using Raman spectroscopy, this cation–π interaction is directly observed for the first time. DFT modeling elucidated the mechanistic factors in this cycloaddition. A teaching experiment was developed based on this mechanistic investigation. Control experiments were employed to demonstrate the testing of two alternative mechanistic hypotheses. Cyclization reactions were performed with a soluble base (sodium phenoxide) with and without tetrabutylammonium bromide under homogeneous conditions. Students observed that ammonium salt accelerates the reaction. They were encouraged to develop a testable hypothesis for the role of the ammonium salt in the cyclization mechanism: typical phase transfer or other. IR spectroscopy was used to directly observe a dose dependent shift of the alkyne stretching mode due to a cation−π interaction. Undergraduates were able to employ the scientific method on a contemporary system and see how data are generated and interpreted to adjudicate between rival hypotheses in a way that emulates authentic and current research in a lab setting.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00013100
- Subject Headings
- Bicyclic compounds., Ammonium salts., Cycloaddition Reaction.
- Format
- Document (PDF)
- Title
- Synthesis and Characterization of Organotin Polyamine Esters from Diglycine.
- Creator
- Slawek, Paul Peter, Carraher, Charles E., Haky, Jerome E., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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This research is part of a long-term project aimed at elucidating important structural features, of both ligands and metals, that are needed to produce effective anti-cancer agents. The specific goal is the synthesis of organotin polymers containing amino acids, in this case the diamino acid diglycine. The desired materials were synthesized with percent yields ranging from 32-99%. The products were synthesized employing the interfacial polymerization technique. The polymers were then...
Show moreThis research is part of a long-term project aimed at elucidating important structural features, of both ligands and metals, that are needed to produce effective anti-cancer agents. The specific goal is the synthesis of organotin polymers containing amino acids, in this case the diamino acid diglycine. The desired materials were synthesized with percent yields ranging from 32-99%. The products were synthesized employing the interfacial polymerization technique. The polymers were then characterized utilizing the following physical characterization techniques: light scattering photometry (LS), Infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR), and matrix assisted laser desorption mass spectroscopy (MALDI). Physical characterization showed evidence of formation of desired adducts in addition to data that was consistent with the formation of materials containing multiple repeat units. The materials were then analyzed for biological activity. The synthesized materials displayed the ability to inhibit tested cancer cell lines.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00013158
- Subject Headings
- Organotin Compounds, Glycylglycine, Antineoplastic agents--Development
- Format
- Document (PDF)
- Title
- Synthesis of Fluorogenic Probes Specific for Matrix Metalloproteinase 13.
- Creator
- Ibrahim, Mariam, Fields, Gregg B., Leventouri, Theodora, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Matrix Metalloproteinase-13 (MMP-13) belongs to a large family of proteolytic enzymes which are characterized by their ability to degrade the extracellular matrix components. MMP-13 appears to have a critical role in tumor invasion and metastasis. In this study, several fluorogenic probes specific for MMP-13 were designed and characterized. These synthesized probes could be modified with chelators to be applied for imaging MMP-13 in breast cancer and/or multiple myeloma models. The activity...
Show moreMatrix Metalloproteinase-13 (MMP-13) belongs to a large family of proteolytic enzymes which are characterized by their ability to degrade the extracellular matrix components. MMP-13 appears to have a critical role in tumor invasion and metastasis. In this study, several fluorogenic probes specific for MMP-13 were designed and characterized. These synthesized probes could be modified with chelators to be applied for imaging MMP-13 in breast cancer and/or multiple myeloma models. The activity and selectivity of MMP-13 and other MMPs against these probes were studied through two approaches. It was found that these probes were cleaved by all MMPs, but MMP-13 showed the highest activity and selectivity towards these peptides.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013507
- Subject Headings
- Matrix Metalloproteinases, Peptides, Fluorogenic probes
- Format
- Document (PDF)
- Title
- Synthesis and photophysical measurements of a series of lanthanide-benzenedicarboxylate coordination polymers.
- Creator
- Clark, Jessica Montressa., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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Within solid-state chemistry, coordination polymers have gained interest for use in various applications such as sensing, catalysis, display technology, hydrogen storage, etc. The use of lanthanide ions in these materials provides a mean of exploring how structure may affect luminescence efficiency. In this study, the photophysics of several lanthanide benzenecarboxylates was studied. This data combined with data from other coordination polymers created in our lab indicate that the...
Show moreWithin solid-state chemistry, coordination polymers have gained interest for use in various applications such as sensing, catalysis, display technology, hydrogen storage, etc. The use of lanthanide ions in these materials provides a mean of exploring how structure may affect luminescence efficiency. In this study, the photophysics of several lanthanide benzenecarboxylates was studied. This data combined with data from other coordination polymers created in our lab indicate that the established guidelines for producing highly efficient materials may not correlate directly from solution to the solid state and that structure may also play a role.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3362332
- Subject Headings
- Rare earth metals catalysts, Metallic composites, Speciation, Lanthanide shift reagents, Organic compounds, Synthesis, Polymers, Biotechnology
- Format
- Document (PDF)