Development of a Divergent Route to Erythrina Alkaloids

Sebastian Clementson; Mikkel Jessing; Paulo J. Vital; Jesper L. Kristensen

doi:10.1055/s-0039-1690792

Synlett, Table of Contents

Synlett 2020; 31(04): 327-333
DOI: 10.1055/s-0039-1690792

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Development of a Divergent Route to Erythrina Alkaloids

Sebastian Clementson

^aMolecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark

^bDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark Email: jesper.kristensen@sund.ku.dk

,

Mikkel Jessing

^aMolecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark

,

Paulo J. Vital

,

Jesper L. Kristensen ∗

^bDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark Email: jesper.kristensen@sund.ku.dk

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Abstract

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Abstract

Erythrina alkaloids were identified at the end of the 19th century and today, more than 100 members of the erythrinane family have been isolated. They are characterized by a unique tetracyclic, α-tertiary spiroamine scaffold. Herein we detail our efforts towards the development of a divergent enantioselective synthesis of (+)-dihydro-β-erythroidine (DHβE) – one of the most prominent members of this intriguing family of natural products.

1 Introduction

2 Synthetic Strategy

2.1 First Generation

2.2 Second Generation

2.3 Third Generation

2.3.1 Radical Endgame

2.3.2 Completion of the Total Synthesis

3 Conclusion

Key words

Erythrina alkaloids - total synthesis - asymmetric allylic alkylation - ring closing metathesis - decarboxylative cross coupling - spiroamine

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References

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