Browsing by Subject "Phomopsichalasin"
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Item Biosynthetic studies of ottelione A and the structural re-analysis of the "Jones isomers"; the structural reassignment of Phomopsichalasin to that of Diaporthichalasin(2013-02) Brown, Susan G.Part 1 Ottelione A, isolated from the fresh water plant Ottelia alismoides, is a cytotoxic agent at nanomolar levels against 60 human cancer cell lines. Among other compounds isolated were a group of novel 1,7-diarylheptanoids. We propose that one of these diarylheptanoids shares a biogenetic linkage with ottelione A. Namely, we hypothesize that a spontaneous (i.e., non-enzyme catalyzed) Cope rearrangement, almost entirely unprecedented in nature, is central to the biosynthesis of ottelione A. The successful synthesis of the hypothesized biologically relevant diarylheptanoid has now enabled us to probe its possible biogenetic linkage to ottelione A. During the course of our studies we have also performed the structure reanalysis of two related hydrienone compounds that share the exact same core as ottelione A. Part II Phomopsichalasin, a cytochalasin-like secondary metabolite, was isolated from an endophytic fungus Phomopsis sp. in 1995. Diporthichalasin, from the endophytic fungus Diaporthe sp. Bkk3, was isolated several years later in 2007. Both were assigned different structures and their spectroscopic characterization reported in two different solvents. By way of detailed NMR analysis and pertinent computational models we have demonstrated that the structure originally proposed for Phomopsichalasin was incorrect and is in fact that of the more recently isolated compound Diaporthichalasin.Item Second generation synthesis of UCS1025A. synthetic efforts toward total syntheses of CJ-16,264 and Phomopsichalasin.(2009-06) Sizova, Elena P.The present work consists primarily of the four projects. The first is methodology for silyl triflate-mediated Dieckmann-like cyclization between esters and imides. The second project is the second generation synthesis of a natural product UCS1025A, which included optimization of the synthesis of the triene precursor of UCS1025A and exploration of its biomimetic Intra-Molecular Diels-Alder (IMDA) cycloaddition. A more efficient way to synthesize the corresponding triene via the MeMgBr-mediated addition of the corresponding vinyl iodide to the enal and optimization of the diastereoselectivity of the final Diels-Alder-cycloaddition to produce UCS1025A are described. The third project, described in Chapter II, is synthetic efforts toward total synthesis of the related natural product CJ-16,264. We have studied the diastereoselective IMDA cycloaddition of the corresponding chiral aldehyde precursor in the presence of MacMillan catalyst followed by BEt3-promoted Reformatski-coupling with iodolactones in the synthesis of various diastereomeric analogs of CJ-16,264. The final project, described in Chapter III, is the synthetic efforts total synthesis of the natural products phomopsichalasin and diaporthichalasin, which we envision to be biosynthesized via a series of two sequential and spontaneous IMDA cycloadditions. Several approaches to the heterocyclic portion of the natural products and their tetraene precursor are described.Item A unified strategy for penostatin (Bio)synthesis and forays in computational chemistry(2012-07) Jansma, Matthew JamesPART 1: Comprising Chapters I–IV, the studies described in the first part of this Thesis have as their overarching goal the utilization of organic synthesis to address questions of biosynthetic import. The impetus for this work has been provided by the penostatins A–I, a family of biologically active, structurally atypical, polyketide-derived secondary metabolites isolated from the fungus Penicillium sp. OUPS-79. Critical mechanistic and structural analyses have compelled the hypothesis that the penostatins arise via spontaneous (i.e., non enzyme-catalyzed) pericyclic reaction cascades that emanate from a single biogenetic precursor. Part 1 is inaugurated with a concise summary of the isolation, structure determination, and biological activity of the penostatins (Chapter I). In addition, a discussion of others' previous synthetic efforts toward members of the family is presented. Chapter II describes a campaign that has culminated in the stereoselective synthesis and study of the putative biosynthetic precursor to penostatins A and B, which constitutes the vast majority of the work conducted during the author's tenure. A pertinent model study that involved the design, synthesis, and subsequent investigation of (the enolates derived from) a pair of model dihydropyran substrates is detailed in Chapter III. This work has tentatively supported the notion that penostatins I and F arise via spontaneous [3,3]-sigmatropic (Claisen) rearrangements. Finally, Chapter IV documents progress toward the synthesis of a model substrate relevant to the biosynthesis of penostatins G and H. PART 2: The ability to reliably deduce the constitution and relative configuration of newly isolated organic molecules lies at the very core of all endeavors in the fields of synthetic organic and natural products chemistry. Nuclear magnetic resonance (NMR) spectroscopy is unarguably the single most powerful spectroscopic tool for this task; however, the unambiguous assignment of these structural properties via spectroscopic data alone is rarely a trivial matter. In Part 2 of this Thesis, the power and utility of DFT-based computational methods for the structure determination of small organic molecules are showcased. Chapter V includes a short discussion of the motivation for these studies and previous work from the Hoye/Cramer team. Then, in Chapter VI, computed proton (1H) and carbon (13C) NMR chemical shifts (δ) are employed to address structural issues that have arisen from two concurrent synthetic endeavors in the Hoye group. On the basis of the computational results described therein, reassignments of (i) the structures of the ‘Jones isomers’ and (ii) the relative configuration within (at least) the AB ring system of phomopsichalasin are strongly recommended. Additionally, a reexamination of the reported 1H NMR chemical shift assignments for patchouli alcohol has emerged from a collaborative effort with the Cramer group.