Synlett 2017; 28(17): 2212-2229
DOI: 10.1055/s-0036-1588851
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© Georg Thieme Verlag Stuttgart · New York

Lycopodium Alkaloids: An Intramolecular Michael Reaction Approach

Mrinmoy Saha*
,
Rich G. Carter*
Financial support for this research was provided by the National Science Foundation (CHE 1363105).
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Publikationsverlauf

Received: 28. Februar 2017

Accepted after revision: 03. Mai 2017

Publikationsdatum:
06. Juni 2017 (online)


Abstract

The Lycopodium alkaloids possess a rich history that has captured the attention of synthetic chemists across the globe. This large family consists of over 250 known natural products with diverse structural features and noteworthy biological activity. Herein, we interweave the synthetic accomplishments by others in the field with our own unified strategy to accessing multiple subfamilies of the Lycopodium alkaloids. This discussion includes lycopodine, the C10-hydroxy Lycopodium alkaloids (10-hydroxylycopodine, deacetylpaniculine and paniculine), pelletierine, cermizine D, fastigiatine, himeradine A, clavolonine and 7-hydroxylycopodine. A unifying feature of much of the work discussed within this account is the use of intramolecular Michael additions to construct key ring systems within the Lycopodium alkaloids. Examples include the use of an intramolecular keto-sulfone Michael reaction and an intramolecular heteroatom Michael reaction.

1 General Background on Lycopodium Alkaloids

2 Development of a Strategy for Lycopodium Alkaloids

2.1 Generalized Strategy

2.2 Known Syntheses of C10-Functionalized Lycopodium Alkaloids

3 Quinolizidine-Type Alkaloids

3.1 Background

3.2 Development of the Heteroatom Michael Reaction

3.3 Synthesis of the Core Lycopodine Building Block: Pelletierine

3.4 Total Synthesis of Cermizine D

3.5 Synthesis of the Eastern Half of Himeradine A

4 Lycopodine-Type Alkaloids

4.1 Total Syntheses of Lycopodine

4.1.1 Earlier Racemic Syntheses

4.1.2 Approach Toward the Tricyclic Skeleton of Lycopodine: Intramolecular Mannich

4.1.3 Enantioselective Total Syntheses of Lycopodine

4.2 Total Syntheses of Clavolonine (8-Hydroxylycopodine)

4.3 Total Synthesis of 7-Hydroxylycopodine

4.4 Synthetic Route for 10-Hydroxy Lycopodium Alkaloids

4.4.1 Background

4.4.2 Total Syntheses

4.4.3 Impact of the C10-Stereochemistry

5 Conclusion