Ancistrocladus Naphthylisoquinoline Alkaloids

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

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  

2.3 A Novel Biosynthesis Pathway in Plants: Acetogenic  

2.4 The Tool Box Used for the Isolation, Structural Elucidation, and  

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  

3.3 Ancistrocladus griffithii from Submontane Forests in the  

West and South of Southeast Asia   …………………………………………….

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  

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 

4.3 Directed Synthesis of Ancistrocladisine via Configurationally  

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  

4.7 A Series of 7,3'-Coupled Naphthylisoquinoline Alkaloids Isolated  

4.8 Ancisheynine A, a Novel-Type N,C-Coupled Naphthylisoquinolinium  

Alkaloid: Total Synthesis and Stereoanalysis   …………………..……………

4.9.1 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   ……...

5.1.1 Characterization of Mono- and Dimeric Naphthylisoquinoline  

Alkaloids by HPLC-ESI-MS/MS   ………………………………..…………….

Alkaloids by HPLC-NMR   …………………………………………..…………

5.1.3 Online Assignment of Absolute Configurations of  

5.2 A Photometric Chemical Screening Method to Trace Up  

5.3 Online-Discovery of the First Ancistrocladaceae-Type Dimer  

by the LC-MS/MS/LC-NMR/LC-ECD Triad   …………………………....…....

Monomeric Naphthylisoquinoline Alkaloids Online, Directly from   

Ancistrocladus griffithii   ……………………………………..…………………

Unprecedented Series of Non-Hydrogenated Ancistrocladaceae- and   

Dioncophyllaceae-Type Naphthylisoquinoline Alkaloids   ………..……….......

6.1 Ancistrobenomine A, the First Naphthylisoquinoline Alkaloid with a  

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 Taxon? — Metabolite Pattern und Phylogenetic   

Relationship to Ancistrocladus aff. tectorius from China   …………....……….

7.1 In the Leaves of Ancistrocladus cochinchinensis: Predominant  

7.2 7-epi-Ancistrobrevine D and Related 7,1'-Coupled  

Naphthyltetrahydroisoquinoline Alkaloids   ………………….………………..

Online, by LC-MS/MS-NMR-ECD: Ancistrocladinium A and Two   

New Phenolic Analogues   ……………………………………………….…..…

7.4 Biosynthetically Related, Mostly Non-Coupled Naphthoquinones,  

7.5 Phytochemical Relationship of Ancistrocladus cochinchinensis and  

Ancistrocladus aff. tectorius from the Chinese Island of Hainan   ……….…….

Wid