Isolation and Synthesis of Veranamine, an Antidepressant Lead from the Marine Sponge Verongula rigida

Anna J Kochanowska-Karamyan; Hugo C Araujo; Xiong Zhang; Abir El-Alfy; Paulo Carvalho; Mitchell A Avery; Stephen D Holmbo; Jakob Magolan; Mark T Hamann

doi:10.1021/acs.jnatprod.9b01107

Isolation and Synthesis of Veranamine, an Antidepressant Lead from the Marine Sponge Verongula rigida

J Nat Prod. 2020 Apr 24;83(4):1092-1098. doi: 10.1021/acs.jnatprod.9b01107. Epub 2020 Mar 31.

Authors

Anna J Kochanowska-Karamyan^{1

2}, Hugo C Araujo³, Xiong Zhang^{4

3}, Abir El-Alfy^{1

5}, Paulo Carvalho^{1

6}, Mitchell A Avery¹, Stephen D Holmbo³, Jakob Magolan^{4

3}, Mark T Hamann^{1

7}

Affiliations

¹ Departments of Pharmacognosy and Pharmacology, National Center for Natural Products Research, University of Mississippi, University Park, Mississippi 38677, United States.
² Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University HSC, Amarillo, Texas 79106, United States.
³ Department of Chemistry, University of Idaho, Moscow, Idaho 83844, United States.
⁴ Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.
⁵ Department of Biopharmaceutical Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
⁶ Feik School of Pharmacy, University of the Incarnate Word, San Antonio, Texas 78209, United States.
⁷ Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, United States.

PMID: 32227883
DOI: 10.1021/acs.jnatprod.9b01107

Abstract

The natural product veranamine was isolated from the marine sponge Verongula rigida. It contains a unique heterocyclic scaffold and demonstrates in vivo antidepressant activity and selective affinity for 5HT2B and sigma-1 receptors. The first total synthesis of veranamine is reported. Our scalable synthesis offers veranamine in six steps and 25% yield via an unprecedented vinylogous Pictet-Gams pyridine formation strategy. Veranamine is a promising new lead compound for antidepressant drug development.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Antidepressive Agents / chemistry
Antidepressive Agents / isolation & purification
Antidepressive Agents / pharmacology*
Molecular Structure
Porifera / chemistry*

Substances

Antidepressive Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding