Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products, Vol. 93 (Fortschritte der Chemie organischer Naturstoffe ... the Chemistry of Organic Natural Products)

Lignans, by convention, are a group of natural products that are formed by linking two phenylpropanoid units (C C units) by oxidative coupling. Most importantly, in 6 3 a lignan, two (C C units) are bound through the central carbon of their side chains, 6 3 0 i. e. the 8 and 8 positions (1, 2). The occurrence of C C -dimers, linked at sites other 6 3 0 than the 8–8 positions, is also known and these compounds have been termed neolignans (3, 4). As these two groups of compounds have close structural as well as biosynthetic relationships, they are often associated together and incorporated under the general term “lignan” (5). The diverse structural categorization of true lignans and of a few neolignans is presented in Fig. 1. Through the years, several review articles or books covering different facets of lignans, including their ch- istry (6, 7), biogenesis (8), synthesis (9), and biological activities (10) have been published. Enduring research for the investigation of secondary metabolites of plants has evidenced some compounds that are biogenetically related to true lignans or neolignans but bear some features not discerned in conventional lignans. These compounds or groups of compounds have been termed as “non-conventional lignans”, and include coumarinolignans, ?avonolignans, and stilbenolignans. The non-conventional lignans, like the conventional ones, have two C C units linked 6 3 together but have additional structural features to place them also under the category of coumarins, ?avonoids, or stilbenes. Cover 1 Progress in the Chemistry of Organic Natural Products, Vol. 93 (Springer, 2010) 4 ISBN 978-3-7091-0139-1 5 Contents 6 Contributors 8 Non-conventional Lignans: Coumarinolignans, Flavonolignans, and Stilbenolignans 16 Introduction 17 Coumarinolignans 18 Occurrence of Coumarinolignans 18 Classification of Coumarinolignans 20 Structure Elucidation of Coumarinolignans 22 Ultraviolet Absorption Spectra and Infrared Spectra 22 1H NMR Spectra 22 13C NMR Spectra 23 Additional NMR Observations 23 Mass Spectra 26 Optical Activity 27 Chemistry of Coumarinolignans 29 Cleomiscosins 30 Venkatasin and Hyosgerin 33 Antidesmanins 35 Grewin 35 Synthesis of Coumarinolignans 36 Biological Activity of Coumarinolignans 40 Biogenesis of Coumarinolignans 42 Flavonolignans 43 Occurrence of Flavonolignans 44 Features of Flavonolignans and Their Classification 44 Structure Elucidation of Flavonolignans 48 Ultraviolet Absorption Spectra and Infrared Spectra 48 1H NMR Spectra 48 13C NMR Spectra 50 Mass Spectra 50 Circular Dichroism Spectra 51 X-ray Crystallographic Analysis 53 Chemistry of Flavonolignans 53 Silybins 53 Aegicin and Related Flavonolignans 60 Cyclohexane Bridged Flavonolignans 62 Biological Activity of Flavonolignans 63 Biogenesis of Flavonolignans 64 Stilbenolignans 65 Occurrence and Features of Stilbenolignans 65 Structure Elucidation and Synthesis of Stilbenolignans 67 Aiphanol 68 Gnetofuran A and Gnetucleistol F 74 Gnetifolin F and Related Stilbenolignans 74 Biological Activity of Stilbenolignans 76 Biogenesis of Stilbenolignans 77 References 79 Picrotoxanes 86 Introduction 87 Tabular Overview of the Picrotoxanes 88 Occurrence 123 Systematic and Geographic Occurrence of Picrotoxane-Containing Plants 123 Menispermaceae 123 Coriariaceae 123 Picrodendraceae and Phyllanthaceae (Formerly Euphorbiaceae) 124 Orchidaceae 124 Parasitic Plants 125 Convolvulaceae 125 Loranthaceae 125 Picrotoxanes Found in Animals and Animal Products 125 The Riddle of the Scattered Taxonomic Occurrence of Picrotoxanes 126 Isolation of Picrotoxanes 126 Examples of Recent Isolation Procedures 127 Isolation from M. cocculus (A. cocculus) 127 Isolation from the Sponge S. inconstans (C. inconstans) 127 Isolation from Coriaria Species 127 Isolation from the Parasitic Plant Loranthus parasiticus 128 Isolation from Toxic Honey and Quantitative Analysis of its Main Picrotoxanes 128 Isolation from Hyenanche globosa 129 Isolation from Picrodendron baccatum 129 Isolation from Dendrobium Species 131 Structure Determination of Picrotoxanes 132 Main Picrotoxanes of the Menispermaceae 132 Picrotoxinin 132 Picrotin 133 Main Picrotoxanes of the Coriariaceae 134 Coriamyrtin and Tutin 134 Corianin 134 Picrotoxanes Isolated from Toxic Honey 136 Picrotoxanes of the Picrodendraceae 136 Picrotoxanes of H. globosa 136 Picrotoxanes of P. baccatum and Three Related Structures 138 Picrodendron A and its One-Dimensional NMR Spectra 138 Picrodendrins B, C, D, I, J, and G and the Use of NOE in the Structure Determination of Picrotoxanes 139 Picrodendrins E, F, L-T, and Celaenodendrolide I 140 Picrodendrins with Fused gamma-Lactones 141 Picrodendrins from the Leaves of P. baccatum, Picrotoximaesin and Asteromurin A 142 Picrotoxanes from Dendrobium Species 142 Dilactones 142 Monolactones and Structurally Deviant Picrotoxanes 143 The Dendrobines, Sesquiterpene Alkaloids 144 Dendrobinium Salts, Quaternary Sesquiterpene Alkaloids 147 Total Syntheses of Picrotoxanes 149 Overview 149 Syntheses of Dendrobines 149 Syntheses of Sesquiterpene Picrotoxanes 152 Description of the Syntheses 153 Syntheses of Dendrobine 153 Synthesis of the Skeleton of Dendrobine by Kaneko et al. 153 Total Synthesis of ()-Dendrobine by Yamada et al. 154 Synthesis of 2-Hydroxydendrobine and Nobilonine by Yamada et al. 156 Total Synthesis of ()-Dendrobine by Inubushi et al. 156 A Simple Total Synthesis of ()-Dendrobine by Kende et al. 158 Synthesis of 4-Epi-Dendrobine by Borch et al. 160 Total Synthesis of ()-Dendrobine by Roush 162 Two of the Attempted Syntheses of ()-Dendrobine by Heathcock et al. 165 A Formal Synthesis of ()-Dendrobine by Martin et al. 168 An Efficient Total Synthesis of ()-Dendrobine by Livinghouse et al. 168 A Facile EPC-Approach to the Dendrobine Skeleton by Takano et al. 170 Formal Total Synthesis of ()-Dendrobine by Trost et al. 171 Formal Total Synthesis of (-)-Dendrobine by Mori et al. 173 First Total EPC-Synthesis of (-)-Dendrobine by Sha et al. 175 Formal Total Synthesis of (-)-Dendrobine by Zard et al. 176 Formal Total Synthesis of ()-Dendrobine by Padwa et al. 177 Syntheses of Sesquiterpene Picrotoxanes 179 Total EPC-Synthesis of Picrotoxinin and Picrotin by Corey et al. 179 Total Synthesis of ()-Coriamyrtin by Inubushi et al. 181 Total Synthesis of (-)-Picrotoxinin and (+)-Coriamyrtin by Yamada et al. 183 First Total Synthesis of (+)-Tutin and (+)-Asteromurin A by Yamada et al. 186 Total EPC-Synthesis of Picrotoxinin and Picrotin by Yoshikoshi et al. 187 Total EPC-Synthesis of Picrotoxinin and Corianin by Trost et al. 189 Partial Synthesis of Corianin by Trost et al. 192 Total Synthesis of Methyl Picrotoxate by Trost et al. 192 A Variant of the Total Syntheses of Corianin by Trost et al. 193 Biosynthesis of Picrotoxanes 195 Investigations on the Biosynthesis of Dendrobines 196 Investigations on the Biosynthesis of Sesquiterpene Picrotoxanes 199 Physiological Activity of Picrotoxanes 203 Toxicity 203 Picrotoxanes Toxic for Humans and Other Mammals 203 Picrotoxanes Toxic for Invertebrates 205 Picrotoxanes as Therapeutics 206 Picrotoxanes as Epileptogenic Compounds 207 Picrotoxanes as Tools in Neurobiological Research 207 References 212 Combinatorial and Synthetic Biosynthesis in Actinomycetes 226 Introduction 226 Combinatorial Biosynthesis and Synthetic Biosynthesis 227 Achievements in Combinatorial Biosynthesis 228 Challenges for Combinatorial Biosynthesis 230 Cloning of Biosynthetic Gene Clusters 230 Heterologous Expression of Biosynthetic Gene Clusters 231 In Silico Techniques to Investigate Natural Products 232 Investigation of Cryptic Secondary Metabolite Gene Clusters Using Computational Analysis and Combinatorial Biosynthesis 233 Comparative Metabolic Profiling 233 Preliminary Bioinformatic Analysis 233 In Vitro Reconstitution 234 Comparative Profiling after Genetic Modification 234 Expression by Incorporation of a Controllable Promoter 234 Metagenomics 235 Rational Design of PKS and NRPS Derived Natural Products 235 Glycodiversification of Natural Products 236 Synthetic Biosynthesis 239 Structural Information for Protein Engineering 242 Directed Evolution and High-Throughput Screening 242 Engineering Enzyme Function 244 References 245 Author Index 253 Subject Index 272 Springer,2010,ISBN 978-3-7091-0139-1,Compiled by MP@GP The volumes of this classic series, now referred to simply as "Zechmeister" after its founder, L. Zechmeister, have appeared under the Springer Imprint ever since the series' inauguration in 1938. The volumes contain contributions on various topics related to the origin, distribution, chemistry, synthesis, biochemistry, function or use of various classes of naturally occurring substances ranging from small molecules to biopolymers. Each contribution is written by a recognized authority in his field and provides a comprehensive and up-to-date review of the topic in question. Addressed to biologists, technologists, and chemists alike, the series can be used by the expert as a source of information and literature citations and by the non-expert as a means of orientation in a rapidly developing discipline Front Matter....Pages i-xv Non-conventional Lignans: Coumarinolignans, Flavonolignans, and Stilbenolignans....Pages 1-70 Picrotoxanes....Pages 71-210 Combinatorial and Synthetic Biosynthesis in Actinomycetes....Pages 211-237 Back Matter....Pages 239-264