FU Berlin Digitale Dissertation
Andreas Sieg : A new synthesis of Zincophorine and synthesis of an enantiopure Cyoctol Eine neue Synthese von Zincophorin
|Abstract| |Table of Contents| |More Information|

Abstract The first part of this Ph.D. thesis describes a novel and convergent strategy to synthesize Zincophorine. This natural polyether antibiotic is of importance in the veterinary medicine. Starting from the commercially available methyl ß-hydroxy isobutyrate three key inter-mediates are generated in 25 steps overall. Evans aldol addition and Evans alkylation serve as key steps to introduce new stereogenic centers with defined configuration. The synthesis of the tetrahydropyrane sub-unit results from a direct regio and diastereoselective cyclization of a 1,5 diol precursor. The coupling of two fragments succeeded via Horner-Wadsworth-Emmons olefination. Twelve of fifteen stereogenic centers of the target Zincophorine are efficiently built-up with high diastereoselectivities. The second part of this thesis describes a novel synthesis of an enantiopure Cyoctol. Starting from the bicyclic core fragment of a carbacycline precursor a range of alkylation methods are investigated to introduce the side chain. The shortest sequence involves a Schlosser Fouquet reaction as the key step allowing to complete the total synthesis in five steps with an overall yield of 37 %.

Table of Contents Download the whole PhDthesis as a zip-tar file or as zip-File For download in PDF format click the chapter title   Titelblatt, Gutachter, Abstract, Danksagung, Inhaltsverzeichnis Teil A  Eine neue Synthese von Zincophorin 1. Einleitung 3 1.1 Einführung und Motivation 3 1.2 Zincophorin 4 2 Literatursynthesen 8 2.1 Totalsynthese nach Danishefsky 8 2.2 Synthese nach Kallmerten 13 2.3 Diastereoselektive Synthese hochsubstituierter THP-Bausteine 17 2.4 Konvergente Synthese komplexer Polyketid-Strukturen 25 2.5 Vergleich der Literatursynthesen: Stärken und Schwächen 27 3 Aufgabenstellung 28 4 Synthesen 28 4.1 Syntheseplanung 28 4.2 Synthese des C1-C9-Fragments (Baustein A) 32 4.3 Synthese des C10-C16-Fragments (Baustein B) 49 4.4 Synthese des C17-C25-Fragments (Baustein C) 52 4.5 Verknüpfung der Bausteine 58 5 Zusammenfassung Teil A 59 Teil B   Synthese einer enantiomerenreinen Cyoctols 6 Einleitung 61 7 Aufgabenstellung 62 8 Synthesen 62 8.1 Synthese des Schlüsselbausteins 62 8.2 Synthese der Seitenkette 64 8.3 Die Schlosser-Fouquet-Kupplung 65 8.4 Die Sulfonkupplung 68 9 Zusammenfassung Teil B 70 Experimenteller Teil 10 Methoden 71 10.1 Allgemeine experimentelle Bedingungen 71 10.2 Chromatographie 72 10.3 Instrumentelle Analytik 73 11 Sythesevorschriften und analytische Daten 75 11.1 Synthese verwendeter Reagenzien und Auxiliare 75 11.2 Synthese des C1-C9-Fragments (Baustein A) 82 11.3 Synthese des C10-C16-Fragments (Baustein B) 121 11.4 Verknüpfung der Bausteine 134 11.5 Synthese des C17-C25-Fragments (Baustein C) 136 11.6 Cyoctol-Synthese 148 Anhang Anhang A: Verwendete Akürzungen 161 Anhang B: Nomenklatur 162

More Information:
Online available:	http://www.diss.fu-berlin.de/2001/237/indexe.html
Language of PhDThesis:	german
Keywords:	Zincophorine, Cyoctol, polyketide, polyether, carbacycline
DNB-Sachgruppe:	30 Chemie
Date of disputation:	22-Dec-2000
PhDThesis from:	Fachbereich Biologie, Chemie, Pharmazie, Freie Universität Berlin
First Referee:	Prof. Dr. Johann Mulzer
Second Referee:	Prof. Dr. Hans-Ulrich Reissig
Contact (Author):	asieg@gmx.de
Contact (Advisor):	mulzer@felix.orc.univie.ac.at
Date created:	28-Nov-2001
Date available:	28-Nov-2001

 

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