Ancistrocladus Naphthylisoquinoline Alkaloids

ISBN-13: 9783031104565 / Angielski / Twarda / 2023 / 335 str.

A. Douglas Kinghorn; Heinz Falk; Simon Gibbons

Opis

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.

Spis treści

Contents

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   ……………………………………………………………..

1. 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   ……………….…

1. 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   ……………………………………………………………………………..