This book describes a unique class of secondary metabolites, the mono- and dimeric-naphthylisoquinoline alkaloids. They exclusively occur in lianas of the palaeotropical Ancistrocladaceae and Dioncophyllaceae plant families. Their unprecedented structures include stereogenic centers and rotationally hindered, and therefore stereogenic, axes. Extended recent investigations on six Ancistrocladus species from Asia, as reported in this contribution, shed light on their fascinating phytochemical productivity, with over 100 intriguing natural products. This high chemodiversity arises from a similarly unique biosynthesis from acetate-malonate units, following a novel polyketidic pathway to plant-derived isoquinoline alkaloids. Some of the compounds show most promising anti-parasitic activities. Additionally, strategies for the regio- and stereoselective total synthesis of the alkaloids, including the directed construction of the chiral axis, are also presented.
Author(s): A. Douglas Kinghorn, Heinz Falk, Simon Gibbons, Yoshinori Asakawa, Ji-Kai Liu, Verena M. Dirsch
Series: Progress in the Chemistry of Organic Natural Products, 119
Publisher: Springer
Year: 2023
Language: English
Pages: 343
City: Cham
About This Book
Contents
Contributors
1 Asian Ancistrocladus Lianas as Creative Producers of Naphthylisoquinoline Alkaloids
1 Introduction
2 Naphthylisoquinoline Alkaloids, a Fascinating Class of Axially Chiral Biaryl Natural Products
2.1 Structural Diversity and Classification of Naphthylisoquinoline Alkaloids—A Short Overview
2.2 Mono- and Dimeric Dioncophyllaceae-Type Naphthylisoquinolines and Related Compounds
2.2.1 Occurrence of Dioncophyllaceous Alkaloids in Nature
2.2.2 Artificial Dimers of Dioncophyllaceae-Type Monomers as Promising Antiplasmodial Agents: Design and Total Synthesis
2.3 A Novel Biosynthesis Pathway in Plants: Acetogenic Naphthylisoquinoline Alkaloids
2.4 The Tool Box Used for the Isolation, Structural Elucidation, and Stereochemical Assignment of Naphthylisoquinoline Alkaloids—A Short Overview
3 Ancistrocladus, a Genus of Woody Lianas of the Monotypic Plant Family Ancistrocladaceae Widely Occurring in India, Sri Lanka, and Southeast Asia
3.1 Ancistrocladus heyneanus, a Large Climbing Shrub from the Indian Subcontinent
3.2 Ancistrocladus hamatus, Endemic to the Lowland Evergreen Forests of Sri Lanka
3.3 Ancistrocladus griffithii, from Submontane Forests in the West and South of Southeast Asia
3.4 Ancistrocladus attenuatus, from Lowland Evergreen Forests of Myanmar and the Indian Andaman Islands
3.5 Ancistrocladus benomensis, a New Submontane Liana from Peninsular Malaysia
3.6 Ancistrocladus tectorius, Widely Distributed in the Rain Forests All Over Southeast Asia
4 The Indian Liana Ancistrocladus heyneanus and Ancistrocladus hamatus from Sri Lanka: Early Studies and More Recent Discoveries
4.1 Ancistrocladine and Further 5,1′-Coupled Naphthylisoquinoline Alkaloids from the Roots and Leaves of Ancistrocladus heyneanus
4.2 Directed Total Synthesis of Ancistrocladine and Its Atropo-Diastereomer Hamatine by the Lactone Methodology
4.3 Directed Synthesis of Ancistrocladisine via Configurationally Unstable Lactone-Bridged Biaryl Lactones
4.4 Total Synthesis of Ancistrocladidine by ortho-Arylation of a Naphthol with an Aryllead Triacetate
4.5 Atroposelective Total Synthesis of Enantiomerically Pure Ancistrocladidine and Ancistrotectorine Using the Lactone Method
4.6 Produced in Aging Shoots and in Cell Cultures of Ancistrocladus heyneanus, The 7,8′-Coupled Naphthylisoquinoline Alkaloid Ancistroheynine A and Further Stress Metabolites
4.7 A Series of 7,3′-Coupled Naphthylisoquinoline Alkaloids Isolated from Fresh Leaves of Ancistrocladus heyneanus
4.8 Ancisheynine, a Novel-Type N,C-Coupled Naphthylisoquinolinium Alkaloid: Total Synthesis and Stereoanalysis
4.9 Simplified N,C-Coupled Arylisoquinolinium Salts as Promising Candidates for the Development of Antiparasitic Agents
4.9.1 Inhibitory Activities of Synthetic Arylisoquinolinium Salts Against Leishmania major
4.9.2 Inhibitory Activities of Synthetic Arylisoquinolinium Salts Against Trypanosoma brucei brucei
4.9.3 Antiplasmodial Activities of Synthetic Arylisoquinolinium Salts and the Formation of Complexes with Hemin
4.9.4 Antibiotic Effects of Dimeric Isoquinolinium Salts on Staphylococcus aureus, Staphylococcus epidermidis and Inhibitory Effects Against Candida albicans
5 Full Absolute Stereostructures of Naphthylisoquinoline Alkaloids Directly from Crude Extracts: Characterization of New Metabolites from Ancistrocladus griffithii by the HPLC-MS/MS-NMR-ECD Triad
5.1 Hyphenation of HPLC with UV, MS, NMR, and ECD
5.1.1 Characterization of Mono- and Dimeric Naphthylisoquinoline Alkaloids by HPLC-ESI-MS/MS
5.1.2 Constitution and Relative Configuration of Naphthylisoquinoline Alkaloids by HPLC-NMR
5.1.3 Online Assignment of Absolute Configurations of Naphthylisoquinoline Alkaloids by HPLC-ECD
5.2 A Photometric Chemical Screening Method to Trace Up Michellamine-Type Naphthylisoquinoline Dimers
5.3 Online Discovery of the First Ancistrocladaceae-Type Dimer, Ancistrogriffithine A, in Crude Leaf Extracts of Ancistrocladus griffithii, by the LC-MS/MS/LC-NMR/LC-ECD Triad
5.4 Complete Structural Elucidation of Ancistrogriffines A–C, Three New Monomeric Naphthylisoquinoline Alkaloids Online, Directly from the Extract of Ancistrocladus griffithii
6 Ancistrocladus benomensis, a New Species from Malaysia, with an Unprecedented Series of Non-hydrogenated Ancistrocladaceae- and Dioncophyllaceae-Type Naphthylisoquinoline Alkaloids
6.1 Ancistrobenomine A, the First Naphthylisoquinoline Alkaloid with a Hydroxymethylene Function at C-3, and Related 5,1′-Coupled Compounds
6.2 Discovery of the First Dioncophyllaceae-Type Naphthylisoquinoline Alkaloids in the Leaves of an Asian Ancistrocladus Species, A. benomensis
6.3 Online Structural Assignment and Observation of the Atropisomerization of the N,6′-Coupled Alkaloid Ancistrocladinium B
6.4 The New Species Ancistrocladus benomensis and Its Extraordinary Chemotaxomic Position Within the Ancistrocladaceae Family
7 Ancistrocladus cochinchinensis from Central Vietnam, a Distinct Ancistrocladus Taxon? Metabolite Pattern and Phylogenetic Relationship to Ancistrocladus aff. tectorius from China
7.1 In the Leaves of Ancistrocladus cochinchinensis: Predominant Occurrence of Naphthylisoquinoline Alkaloids with a 5,1′-Coupling Site
7.2 7-epi-Ancistrobrevine D and Related 7,1′-Coupled Naphthyltetrahydroisoquinoline Alkaloids
7.3 N,8′-Coupled Naphthylisoquinoline Alkaloids Directly Analyzed Online, by LC-MS/MS-NMR-ECD: Ancistrocladinium A and Two New Phenolic Analogues
7.4 Biosynthetically Related, Mostly Non-coupled Naphthoquinones, Tetralones, and Free Isoquinolines from Ancistrocladus cochinchinensis
7.5 Phytochemical Relationship of Ancistrocladus cochinchinensis and Ancistrocladus aff. tectorius from the Chinese Island of Hainan
8 Widespread Throughout Southeast Asia: Ancistrocladus tectorius, a Rich Source of Unique, Structurally Most Diverse Mono- and Dimeric Naphthylisoquinoline Alkaloids
8.1 Evidence for Species Differentiation Within the Ancistrocladus tectorius Complex in Southeast Asia
8.2 Ancistrocladus aff. tectorius from Laos
8.3 Ancistrocladus aff. tectorius from Thailand
8.4 Ancistrocladus aff. tectorius from Malaysia
8.5 Ancistrocladus aff. tectorius from the Chinese Island of Hainan
8.5.1 Ancistrocline from Early Isolation Work and Its Total Synthesis
8.5.2 Further Naphthylisoquinoline Alkaloids with a 5,1′-Coupling Site and Their Broad Structural Diversity
8.5.3 Ancistrotanzanine A and Two Further New Examples of the Rare Subclass of 5,3′-Coupled Naphthylisoquinoline Alkaloids
8.5.4 Ancistrotectoriline A and Related 5,8′-Coupled Naphthylisoquinoline Alkaloids, the Only Five Representatives of this Coupling Type Isolated from an Asian Ancistrocladus Liana
Ancistrotectoriline A and Related Alkaloids
Total Synthesis of Ancistrotanzanine B and Ancistroealaine A by Atroposelective Biaryl Coupling Using Chiral Catalysts
Atroposelective Total Synthesis of 5,8′-Coupled Naphthylisoquinoline Alkaloids Without the Use of an External Chiral Source
8.5.5 Ancistrotectoriline B, Ancistectorines B1 and B2, and Related 7,1′-Coupled Naphthyltetrahydroisoquinoline Alkaloids
8.5.6 Ancistrotectoquinones A and B, Novel-Type Quinoid Natural Products and Related 7,3′-Coupled Naphthylisoquinoline Alkaloids
Ancistrotectorine and Ancistrotanzanine C
Ancistrotectoquinones A and B, the First Alkaloids with a 1,4-Naphthoquinone Portion Coupled to an Isoquinoline Moiety
8.5.7 Ancistrotectoriline C and Ancistrotectorines A and B, the First 7,6′-Coupled Ancistrocladaceae-Type Naphthylisoquinoline Alkaloids
8.5.8 Ancistectorine C1, the Only Known Example of a 7,8′-Coupled Naphthylisoquinoline Alkaloid Isolated from A. aff. tectorius
8.5.9 N,C-Coupled Naphthyldihydroisoquinolinium Alkaloids: Ancistrocladinium A and B and Related Compounds
Occurrence of Ancistrocladinium A Together with Its Mono- and Bisphenolic Analogues
First Total Synthesis of Ancistrocladinium A and B and the Related, as Yet Unnatural N,3′-Coupled Analogue Ancistrocladinium C, Starting from the Chiral Pool
Again Starting from the Chiral Pool: Directed Synthesis of All Four Pure Stereoisomers of Ancistrocladinium A
Directed Synthesis of the Pure Atropo-Diastereomers of the Unnatural N,1′-Coupled Naphthylisoquinoline Ancistrocladinium D, Starting from the Chiral Pool
Synthesis of the Stereoisomers of Ancistrocladinium A with Catalytic Enantioselective Construction of C-3
8.5.10 Ancistrocyclinones A and B, Unprecedented Pentacyclic N,C-Coupled Naphthylisoquinoline Alkaloids
8.5.11 Shuangancistrotectorines A–E, Dimeric Naphthylisoquinoline Alkaloids with Three Consecutive Chiral Biaryl Axes
9 Tables of the Naphthylisoquinoline Alkaloids and Related Compounds Isolated from Asian Ancistrocladus Species
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