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Isolation and Semi-synthesis of Marine Diterpenoids

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Date Issued:
2020
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 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.
Title: Isolation and Semi-synthesis of Marine Diterpenoids.
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Name(s): Scesa, Paul D., author
West, Lyndon, Thesis advisor
Florida Atlantic University, Degree grantor
Department of Chemistry and Biochemistry
Charles E. Schmidt College of Science
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Date Created: 2020
Date Issued: 2020
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: online resource
Extent: 739 p.
Language(s): English
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 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.
Identifier: FA00013539 (IID)
Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2020.
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Includes bibliography.
Subject(s): Marine natural products
Diterpenoids
Biomimetics
Held by: Florida Atlantic University Libraries
Sublocation: Digital Library
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00013539
Use and Reproduction: Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Use and Reproduction: http://rightsstatements.org/vocab/InC/1.0/
Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.