Akuammicine is a

monoterpene Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear (acyclic) or contain rings (monocyclic and bicyclic). Modified terpenes, such as those containing oxygen funct ...

indole alkaloid Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known differe ...

of the

Vinca ''Vinca'' (; Latin: ''vincire'' "to bind, fetter") is a genus of flowering plants in the family Apocynaceae, native to Europe, northwest Africa and southwest Asia. The English name periwinkle is shared with the related genus ''Catharanthus'' (an ...

sub-group. It is found in the

Apocynaceae Apocynaceae (from ''Apocynum'', Greek for "dog-away") is a family of flowering plants that includes trees, shrubs, herbs, stem succulents, and vines, commonly known as the dogbane family, because some taxa were used as dog poison Members of the ...

family of plants including ''

Picralima nitida ''Picralima'' is a plant genus in the family Apocynaceae, first described as a genus in 1896. It contains only one known species, ''Picralima nitida'', native to tropical Africa (Benin, Ghana, Ivory Coast, Nigeria, Gabon, Cameroon, Cabinda, Cent ...

'', ''

Vinca minor ''Vinca minor'' (common names lesser periwinkle or dwarf periwinkle) is a species of flowering plant in the dogbane family, native to central and southern Europe, from Portugal and France north to the Netherlands and the Baltic States, east to ...

'' and the ''

Aspidosperma ''Aspidosperma'' is a genus of flowering plant in the family Apocynaceae, first described as a genus in 1824. It is native to South America, Central America, southern Mexico, and the West Indies The West Indies is a subregion of North A ...

''.

History

The

alkaloids Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar st ...

are a large group of

natural products A natural product is a natural Chemical compound, compound or chemical substance, substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural product ...

which are classified according to the part-structure which members of a particular group contain. Akuammicine is a monoterpene indole alkaloid of the Vinca sub-group which shares a common

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

with other members, namely that they are derived from

strictosidine Strictosidine is a natural chemical compound and is classified as a glucoalkaloid and a vinca alkaloid. It is formed by the Pictet–Spengler condensation reaction of tryptamine with secologanin, catalyzed by the enzyme strictosidine synthase. ...

. It was first isolated in 1927 and had been investigated by Sir Robert Robinson and others before its structure was correctly deduced. This was confirmed by

X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...

in 2017.

Natural occurrence

Akuammicine is found in plants of the

family and was first isolated from ''

''. It has also been reported in ''

Catharanthus roseus ''Catharanthus roseus'', commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a species of flowering plant in the family Apocynaceae. It is native and endemic to M ...

''.

Synthesis

Biosynthesis

As with other indole alkaloids, the biosynthesis of akuammicine starts from the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

. This is converted into strictosidine before further elaboration.

Chemical synthesis

Akuammicine has been a target for

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes ...

, partly because of its relationship to the well-known alkaloid

strychnine Strychnine (, , US chiefly ) is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the eye ...

which has often attracted chemists in academia.

Research

Plant

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s have long been studied for their

biological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...

and alkaloids in particular are major subjects for

ethnobotanical Ethnobotany is the study of a region's plants and their practical uses through the traditional knowledge of a local culture and people. An ethnobotanist thus strives to document the local customs involving the practical uses of local flora for m ...

research. Akuammicine is reported to have effects on

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

uptake and be a κ- and

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical � ...

agonist.

References

{{Reflist Vinca alkaloids Alkaloids found in Apocynaceae