Akuammine

June 21, 2021
I might be a key to developing better opioid medications.
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Akuammine, also known as vincamajoridine, is an indole alkaloid found in the seeds of the akuamma tree (Picralima nitida) that grows in several central African countries. Its alternative name results from its presence in Vinca major, the periwinkle vine that is native to the western Mediterranean.

In 1927, Thomas Anderson Henry* and Thomas Marvel Sharp at the Wellcome Research Laboratories (Beckenham, UK) were the first to isolate akuammine from P. nitida (then called P. klaineana). Later, in 1955, Maurice-Marie Janot and co-workers at the Institute of the Chemistry of Natural Substances (Gif-sur-Yvette, France) showed that the alkaloids isolated from P. nitida and V. major are identical.

P. nitida seeds have been used in traditional medicine to treat pain and fever. Akuammine itself has pharmacological properties, such as antimalarial activity.

This year, a study conducted by Andrew P. Riley at the University of Illinois at Chicago, Richard M. van Rijn, at Purdue University (West Lafayette, IN), and their colleagues showed that akuammine and three similar alkaloids isolated from P. nitida primarily target opioid receptors in the central nervous system of mice. The authors concluded that “their opioid-preferring activity . . . suggest[s] the akuamma alkaloids provide distinct scaffolds from which novel opioids with unique pharmacologic properties and therapeutic utility can be developed.”

No hazard information for akuammine was available at the time of this writing.

Molecule of the future

Molecule of the Future

A current “holy grail” of medicinal scientists is to create an oral medication for COVID-19 patients. Early in the pandemic, the Ebola drug remdesivir from Gilead Sciences (Foster City, CA) was thought to have some benefits and was granted emergency use authorization by the US Food and Drug Administration. But in September 2020, the World Health Organization declared that remdesivir showed no evidence of efficacy and discouraged its use.

But remdesivir isn’t out of the COVID-19 picture yet. Gilead has an inhaled version of the drug in Phase 1 trials; and its scientists are working on an oral version. Their strategy is to make derivatives of the core structure of remdesivir, GS-4415241 (see image), that are more likely to be orally available. Watch this space.

Molecule of the future

Once a month we will bring you a newly discovered or developed molecule that has important implications for the future of chemistry or society in general. Look for it the third week of each month. Learn more about this month's Molecule of the Future below.


Akuammine 
fast facts

CAS Reg. No. 3512-87-6
SciFinder
nomenclature
2H,12H-12a,2,7a-(Epoxyethanylyl-
idene)-indolo-
[2,3-a]-quinol-
izine-15-carboxylic
acid, 3-ethylidene-1,3,4,6,7,12b-
hexahydro-9-
hydroxy-12-methyl-,
methyl ester, (2S,3E,7aS,12aS,
12bS,15R)-
Empirical formula C22H26N2O4
Molar mass 382.45 g/mol
Appearance White crystals
Melting point 255 ºCa (dec)
Water solubility Slight

a. Literature values range from 225 °C to 316 °C.

MOTF update:
June 28, 2021

GS-441524 is the core structure of Gilead Science’s remdesivir. A letter published in Chemical & Engineering News on the same date cites efforts to bring GS-441524 to clinic in 2020. It thus appears that GS-441524 has a past as well as a future.

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