Table Of ContentFortschritte der Chemie
organischer Naturstoffe
Progress in the Chemistry
of Organic Natural Products
Founded by L. Zechmeister
Editors:
A.D. Kinghorn, Columbus, OH
H. Falk, Linz
J. Kobayashi, Sapporo
Honorary Editor:
W. Herz, Tallahassee, FL
Editorial Board:
V.M. Dirsch, Vienna
S. Gibbons, London
N.H. Oberlies, Greensboro, NC
Y. Ye, Shanghai
93
Fortschritte der Chemie
organischer Naturstoffe
Progress in the Chemistry
of Organic Natural Products
Authors:
S.A. Begum, M. Sahai, and A.B. Ray
E. Go¨ssinger
M. Luzhetska, J. Ha¨rle, and A. Bechthold
SpringerWienNewYork
Prof. A. Douglas Kinghorn, College of Pharmacy,
Ohio State University, Columbus, OH, USA
em. Univ.-Prof. Dr. H. Falk, Institut fu¨r Organische Chemie,
Johannes-Kepler-Universita¨t, Linz, Austria
Prof. Dr. J. Kobayashi, Graduate School of Pharmaceutical Sciences,
Hokkaido University, Sapporo, Japan
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Contents
List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Non-conventional Lignans: Coumarinolignans, Flavonolignans,
and Stilbenolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Sajeli A. Begum, Mahendra Sahai, and Anil B. Ray
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Coumarinolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1. Occurrence of Coumarinolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.2. Classification of Coumarinolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.3. Structure Elucidation of Coumarinolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.4. Chemistry of Coumarinolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.5. Biological Activity of Coumarinolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.6. Biogenesis of Coumarinolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3. Flavonolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.1. Occurrence of Flavonolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.2. Features of Flavonolignans and Their Classification . . . . . . . . . . . . . . . . . . 29
3.3. Structure Elucidation of Flavonolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.4. Chemistry of Flavonolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
3.5. Biological Activity of Flavonolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
3.6. Biogenesis of Flavonolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4. Stilbenolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
4.1. Occurrence and Features of Stilbenolignans . . . . . . . . . . . . . . . . . . . . . . . . . . 50
4.2. Structure Elucidation and Synthesis of Stilbenolignans . . . . . . . . . . . . . . . 52
4.3. Biological Activity of Stilbenolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
4.4. Biogenesis of Stilbenolignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
Picrotoxanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Edda Go¨ssinger
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
v
vi Contents
2. Tabular Overview of the Picrotoxanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
3. Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
3.1. Systematic and Geographic Occurrence
of Picrotoxane-Containing Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
3.2. Parasitic Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
3.3. Picrotoxanes Found in Animals and Animal Products . . . . . . . . . . . . . . 110
3.4. The Riddle of the Scattered Taxonomic Occurrence
of Picrotoxanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
4. Isolation of Picrotoxanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
4.1. Examples of Recent Isolation Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
5. Structure Determination of Picrotoxanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
5.1. Main Picrotoxanes of the Menispermaceae . . . . . . . . . . . . . . . . . . . . . . . . . . 117
5.2. Main Picrotoxanes of the Coriariaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
5.3. Picrotoxanes Isolated from Toxic Honey . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
5.4. Picrotoxanes of the Picrodendraceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
5.5. Picrotoxanes from Dendrobium Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
6. Total Syntheses of Picrotoxanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
6.1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
6.2. Description of the Syntheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
7. Biosynthesis of Picrotoxanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
7.1. Investigations on the Biosynthesis of Dendrobines . . . . . . . . . . . . . . . . . 181
7.2. Investigations on the Biosynthesis of Sesquiterpene
Picrotoxanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
8. Physiological Activity of Picrotoxanes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
8.1. Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
8.2. Picrotoxanes as Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
8.3. Picrotoxanes as Epileptogenic Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 192
8.4. Picrotoxanes as Tools in Neurobiological Research . . . . . . . . . . . . . . . . 192
Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Combinatorial and Synthetic Biosynthesis in Actinomycetes . . . . . . . . . . . . . 211
Marta Luzhetska, Johannes Ha¨rle, and Andreas Bechthold
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
2. Combinatorial Biosynthesis and Synthetic Biosynthesis . . . . . . . . . . . . . . . . . . 212
2.1. Achievements in Combinatorial Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . 213
2.2. Challenges for Combinatorial Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . 215
2.3. Synthetic Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Listed in PubMed
Contributors
Andreas Bechthold Institut fu¨r Pharmazeutische Wissenschaften, Lehrstuhl fu¨r
Pharmazeutische Biologie und Biotechnologie der Albert-Ludwigs-Universita¨t
Freiburg, Stefan-Meier-Strasse 19, 79104 Freiburg, Germany
Born in 1978 in Cuddalore, India, Dr. (Mrs) Sajeli A. Begum studied for her
M. Pharm. in Pharmaceutical Chemistry (2001) and performed a chemical investi-
gation into the non-alkaloidal constituents of Solanaceous plants for her doctoral
thesis. She received a Ph.D. in Medicinal Chemistry (2005) from Banaras Hindu
University, Varanasi, India. She is a recipient of a Council of Scientific Industrial
Research (CSIR) – Senior Research Fellowship, India, for her Ph.D. project and a
Deutscher Akademischer Austausch Dienst (DAAD) Fellowship (2004) to pursue
part of her doctoral research at Eberhard Karls Universita¨t, Tu¨bingen, in the group
of Dr. Roderich Suessmuth. Since 2005, she has been working as an assistant
professor in the Department of Pharmaceutics, Institute of Technology, Banaras
Hindu University, and doing research on phytochemical constituents. Her prime
research interests are centered on isolation, structure elucidation, chemical trans-
formation, and pharmacological screening of bioactive natural products. In 2008,
she visited the Indian Institute of Chemical Technology (IICT-CSIR), Hyderabad,
India, through a INSA-Visiting Fellowship.
ix
Dr. Mahendra Sahai received his Master’s degree (Organic Chemistry) from the
University of Gorakhpur in 1972. He joined the laboratory of Professor A.B. Ray in
the Department of Medicinal Chemistry, IMS, Banaras Hindu University, Varanasi,
India, for his Ph.D. work on the chemistry of withasteroids and other natural
products. He obtained his Ph.D. in 1978. He continued his research work in the
laboratory until 1981 as a Research Associate, at CSIR, New Delhi. He then joined
the Weizmann Institute of Science, Israel, as a Postdoctoral Fellow of the Feinberg
Graduate School and worked in the group of Professor Ehud Keinan for a period of
three years in the area of organic synthesis until 1984. In 1984, Dr. Sahai joined the
Department of Medicinal Chemistry of Banaras Hindu University as a lecturer and
subsequently became professor in the year 2004. He is still working in the depart-
ment in the same capacity. He was selected as Visiting Scientist at the TECHNION,
Israel (1988–1990), and worked there on organic synthesis. He received a Centenary
Memorial Fellowship of The Tokyo Institute of Technology, Japan, in the year 1992.
He has worked mainly on the chemistry of natural products and has a total of 82
publications in reputed refereed journals.
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