Main description:

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.

Contents:

Contents

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 .........................................................................................