Description
Book SynopsisThis 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.
Table of ContentsContents
- Introduction …………………………………………………………………..
- 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 ……………………………………………………………..
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 ……………………………………………………..
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, 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 Candida albicans ……………….…
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
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
Chemotaxonomic Position within the Ancistrocladaceae Family …..…….…..
Ancistrocladus cochinchinensis from Central Vietnam, a Distinct
Ancistrocladus Taxon? — Metabolite Pattern und 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 ……….…….
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 …………………………….…...
8.5.5 Ancistrotectoriline B, Ancistrotectorines 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 …….…..
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 …………….…………..
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 ………………………….……….
9.1 5,1'-Coupled Naphthylisoquinoline Alkaloids (Table) ………………………..
9.2 5,3'-Coupled Naphthylisoquinoline Alkaloids (Table) ………………………..
9.3 5,8'-Coupled Naphthylisoquinoline Alkaloids (Table) ……………………….
9.4 7,1'-Coupled Ancistrocladaceae-Type Naphthylisoquinoline
Alkaloids (Table) ………………………………………………………………
9.5 7,1'-Coupled Dioncophyllaceae-Type Naphthylisoquinoline
Alkaloids (Table) ………………………………………………...…………….
9.6 7,3'-Coupled Naphthylisoquinoline Alkaloids (Table) ………………………..
9.7 7,6'-Coupled Naphthylisoquinoline Alkaloids (Table) ………………………..
9.8 7,8'-Coupled Ancistrocladaceae-Type Naphthylisoquinoline
Alkaloids (Table) ………………………………………………………………
9.9 7,8'-Coupled Dioncophyllaceae-Type Naphthylisoquinoline
Alkaloids (Table) ………………………………………………………………
9.10 Naphthylisoquinoline Alkaloids with a 1,4-Naphthoquinone
Portion (Table) ………………………………………………………………...
9.11 Naphthylisoquinoline Alkaloids with a Stereogenic N-Iminium
Aryl Axis (Table) …………………………………………………..………….
9.12 Pentacyclic N,C-Coupled Naphthylisoquinoline Alkaloids (Table) …………..
9.13 Constitutionally Symmetric Ancistrocladaceae-Type
Naphthylisoquinoline Dimers (Table) …………………………………………
9.13.1 6',6''-Dimerized Naphthylisoquinoline Alkaloids (Table) …………………….
9.13.2 3',3''-Dimerized Naphthylisoquinoline Alkaloids (Table) …………………….
9.13.3 1',1''-Dimerized Naphthylisoquinoline Alkaloids (Table) …………………….
9.14 Naphthoquinones and Tetralones Related to Naphthylisoquinoline
Alkaloids (Table) ……………………………………………………………..
9.15 Naphthalene-Devoid Isoquinolines from Asian Ancistrocladus
Species (Table) ……………………………………………………………….
Acknowledgments ……………………………………………………………………..
References ……………………………………………………………………………..
