Naphthylisoquinoline alkaloids [Elektronische Ressource] : structural elucidation, metabolism and functional analysis of their bioactivities / vorgelegt von Johan Henrik Faber

Johan H Faber

Informations

• Publié par: julius-maximilians-universitat_wurzburg
• Publié le: 01 janvier 2007
• Nombre de lectures: 27
• Langue: Deutsch
• Poids de l'ouvrage: 3 Mo

Extrait

Naphthylisoquinoline Alkaloids:
Structural Elucidation, Metabolism,
and Functional Analysis of their
Bioactivities



DISSERTATION ZUR ERLANGUNG DES
NATURWISSENSCHAFTLICHEN DOKTORGRADES
DER BAYERISCHEN JULIUS-MAXIMILIANS-UNIVERSITÄT WÜRZBURG


vorgelegt von
Johan Henrik Faber
aus
Kopenhagen,
Dänemark


Würzburg 2006




Eingereicht am: _______________________________________________________
bei der Fakultät für Chemie und Pharmazie


1. Gutachter: __________________________________________________________
2. Gutachter: __________________________________________________________
der Dissertation


1. Prüfer: _____________________________________________________________
2. Prüfer: _____________________________________________________________
3. Prüfer: _____________________________________________________________
des Öffentlichen Promotionskolloquiums


Tag des Öffentlichen Promotionskolloquiums: ______________________________


Doktorurkunde ausgehändigt am: ________________________________________

Die vorliegende Arbeit wurde in der Zeit von Februar 2002 bis September 2005
am Institut für Organische Chemie der Universität Würzburg angefertigt








Herrn Prof. Dr. Dr. h.c. G. Bringmann danke ich für
die hervorragende Unterstützung dieser Arbeit,
die freundliche Atmosphäre
und die exzellenten Arbeitsbedingungen










Teile der im Rahmen dieser Arbeit erzielten Ergebnisse waren bereits Gegenstand von
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Dedicated to my family
CONTENTS I

Contents
RESULTS AND DISCUSSION..................................................................1
1 Introduction ......................................................................................................................... 1
2 Mode of Action of Quinoline Antimalarial Drugs ............................................................ 7
2.1 UV Spectroscopy........................................................................................................ 8
2.2 Structures of FPIX (9)-Quinoline Antimalarials in Solution .................................... 11
2.3 Further Spectroscopic Investigations........................................................................ 13
3 Isolation and Characterization of Naphthylisoquinoline Alkaloids from
Ancistrocladus tanzaniensis Cheek & Frimodt-Møller (Ancistrocladaceae)...... 15
3.1 Introduction............................................................................................................... 15
3.2 A. tanzaniensis........................................................................................................... 15
3.3 Isolation and Structural Elucidation of Naphthylisoquinoline Alkaloids from A.
tanzaniensis 15
3.3.1 Extraction and Isolation ............................................................................................ 15
3.3.2 Structural Elucidation of Ancistrotanzanine B (13).................................................. 16
3.3.2.1 Spectroscopic Characterization................................................................................. 16
3.3.2.2 The Absolute Configuration...................................................................................... 17
3.3.3 Structural Elucidation of 6-O-Methylancistrocladinine (14) .................................... 19
3.3.3.1 Spectroscopic Characterization 19
3.3.3.2 The Absolute Configuration 20
3.3.4 Structural Elucidation of Ancistrotectoriline (15)..................................................... 21
3.3.4.1 Spectroscopic Characterization................................................................................. 21
3.3.4.2 Absolute Configuration............................................................................................. 22
3.3.5 Isolation and Identification of Ancistrotanzanine C (16).......................................... 23 II CONTENTS
3.3.6 Isolation and Identification of Ancistrotanzanine A (17) ......................................... 23
3.3.7 Isolation and Identification of O,N-Dimethylancistrocladine (18) ........................... 23
3.4 Bioactivity Testing.................................................................................................... 24
3.5 Chemotaxonomic Considerations............................................................................. 25
4 Isolation of Naphthylisoquinoline Alkaloids from a Congolese Ancistrocladus species
Collected in the Habitat Yeteto (Ancistrocladaceae) ........................................... 27
4.1 The Congolese Ancistrocladus Species .................................................................... 27
4.2 Isolation and Structural Elucidation of the Naphthylisoquinoline Alkaloids from the
Leaves of the Congolese Ancistrocladus Species Collected in the Habitat Yeteto .. 27
4.2.1 Introduction............................................................................................................... 27
4.2.2 Extraction and Isolation ............................................................................................ 27
4.2.3 Structural Elucidation of Ancistrocladinium B (22) ................................................. 28
4.2.3.1 Spectroscopic Characterization................................................................................. 29
4.2.3.2 The Absolute Configuration...................................................................................... 31
4.2.3.3 Kinetic Characterization of the Axial Stability of Ancistrocladinium B (22) .......... 34
4.2.3.4 Continuous Characterization Work........................................................................... 36
4.2.4 Isolation and Characterization of Ancistrocladinium A (25).................................... 37
4.3 Bioactivity of the Alkaloids 37
4.4 Isolation and Structural Elucidation of the Naphthylisoquinoline Alkaloids from the
Roots of the Congolese Ancistrocladus Species Collected in the Habitat Yeteto .... 39
4.4.1 Introduction............................................................................................................... 39
4.4.2 Extraction and Isolation ............................................................................................ 39
4.4.3 Structural Elucidation of 5'-O-Demethylhamatine (26)............................................ 39
4.4.3.1 Spectroscopic Characterization................................................................................. 39
4.4.3.2 The Absolute Configuration...................................................................................... 40
4.4.4 Structural Elucidation of 5'-O-Demethylhamatinine (28)......................................... 41
4.4.4.1 Spectroscopic Characterization 41 CONTENTS III

4.4.4.2 The Absolute Configuration...................................................................................... 42
4.4.5 Structural Elucidation of 6-O-Demethylancistroealaine A (30) ............................... 43
4.4.5.1 Spectroscopic Characterization................................................................................. 43
4.4.5.2 The Absolute Configuration 44
4.4.6 Structural Elucidation of 6,5'-O,O-Didemethylancistroealaine A (31)..................... 45
4.4.6.1 Spectroscopic Characterization 45
4.4.6.2 The Absolute Configuration...................................................................................... 46
4.4.7 Structural Elucidation of 5-epi-6-O-Methylancistrobertsonine A (32)..................... 46
4.4.7.1 Spectroscopic Characterization................................................................................. 46
4.4.7.2 The Absolute Configuration 48
4.4.8 Identification and Isolation of Known Naphthylisoquinoline Alkaloids .................. 49
4.5 Bioactivity of the Alkaloids ...................................................................................... 50
4.6 Chemotaxonomic Considerations............................................................................. 51
5 Isolation of Naphthylisoquinoline Alkaloids from Triphyophyllum peltatum
(Dioncophyllaceae) .................................................................................................. 53
5.1 Triphyophyllum peltatum .......................................................................................... 53
5.2 Extraction and Isolation ............................................................................................ 53
5.2.1 Extraction by Soxhlet Apparatus .............................................................................. 53
5.2.2 Fast Centrifugal Partition Chromatography (FCPC)................................................. 54
5.2.3 Preparative HPLC..................................................................................................... 56
5.2.4 Isolation from Roots of T. peltatum ................................................