Synthesis of (+)-7,20-Diisocyanoadociane and Liver-Stage Antiplasmodial Activity of the Isocyanoterpene Class

Hai-Hua Lu; Sergey V Pronin; Yevgeniya Antonova-Koch; Stephan Meister; Elizabeth A Winzeler; Ryan A Shenvi

doi:10.1021/jacs.6b03899

Synthesis of (+)-7,20-Diisocyanoadociane and Liver-Stage Antiplasmodial Activity of the Isocyanoterpene Class

J Am Chem Soc. 2016 Jun 15;138(23):7268-71. doi: 10.1021/jacs.6b03899. Epub 2016 May 31.

Authors

Hai-Hua Lu¹, Sergey V Pronin¹, Yevgeniya Antonova-Koch², Stephan Meister², Elizabeth A Winzeler², Ryan A Shenvi¹

Affiliations

¹ Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
² Department of Pediatrics, University of California, San Diego, School of Medicine , 9500 Gilman Drive 0741, La Jolla, California 92093, United States.

Abstract

7,20-Diisocyanoadociane, a scarce marine metabolite with potent antimalarial activity, was synthesized as a single enantiomer in 13 steps from simple building blocks (17 linear steps). Chemical synthesis enabled identification of isocyanoterpene antiplasmodial activity against liver-stage parasites, which suggested that inhibition of heme detoxification does not exclusively underlie the mechanism of action of this class.

Publication types

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

MeSH terms

Antimalarials / chemical synthesis*
Antimalarials / chemistry
Antimalarials / pharmacology
Heme / metabolism
Liver / parasitology*
Molecular Structure
Nitriles / chemical synthesis*
Nitriles / chemistry
Nitriles / pharmacology
Plasmodium falciparum / drug effects*
Pyrenes / chemical synthesis*
Pyrenes / chemistry
Pyrenes / pharmacology
Stereoisomerism

Substances

Antimalarials
Nitriles
Pyrenes
Heme
diisocyanoadociane

Grants and funding

R01 GM105766/GM/NIGMS NIH HHS/United States