Gramine is a naturally occurring indole

Indole

Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...

 alkaloid

Alkaloid

Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...

 present in several plant species. Gramine may play a defensive role in these plants, since it is toxic to many organisms.

Occurrence

Gramine has been found in the Arundo donax

Arundo donax

Arundo donax, Giant Cane, is a tall perennial cane growing in damp soils, either fresh or moderately saline. Other common names include Carrizo, Arundo, Spanish cane, Wild cane, and Giant reed....

,Acer saccharinum (Silver Maple

Silver Maple

The silver maple —also called creek maple, river maple, silverleaf maple, soft maple, water maple, or white maple—is a species of maple native to eastern North America in the eastern United States and Canada...

), Hordeum

Hordeum

Hordeum is a genus of about 30 species of annual and perennial grasses, native throughout the temperate Northern Hemisphere, temperate South America, and also South Africa....

, and Phalaris

Phalaris (grass)

Phalaris is a genus of grasses. Various species of Phalaris grow on every continent except Antarctica. They can be found in a broad range of habitats from below sea level to thousands of feet above sea level and from wet marshy areas to dry places. P. arundinacea and P...

plant species.

Synthesis

Despite being widely available in several plant species, gramine is far easier to synthesize directly from indole via a Mannich reaction

Mannich reaction

The Mannich reaction is an organic reaction which consists of an amino alkylation of an acidic proton placed next to a carbonyl functional group with formaldehyde and ammonia or any primary or secondary amine. The final product is a β-amino-carbonyl compound also known as a Mannich base...

 with dimethylamine

Dimethylamine

Dimethylamine is an organic compound with the formula 2NH. This secondary amine is a colorless, flammable liquified gas with an ammonia-like odor. Dimethylamine is generally encountered as a solution in water at concentrations up to around 40%...

 and formaldehyde

Formaldehyde

Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...

.

Uses

Gramine is used mostly in synthetic

Chemical synthesis

In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...

 organic chemistry

Organic chemistry

Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...

 as a starting material for tryptophan

Tryptophan

Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

 syntheses.

All reactions of gramine follow the same general reaction scheme. Gramine is reacted with a strong electrophile

Electrophile

In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...

, such as methyl iodide, to form the quaternary ammonium salt 2. The ammonium salt will undergo a Hofmann elimination

Hofmann elimination

Hofmann elimination is a process where an amine is reacted to create a tertiary amine and an alkene by treatment with excess methyl iodide followed by treatment with silver oxide, water, and heat.After the first step, a quaternary ammonium iodide salt is created...

 or Michael addition to give the very active intermediate 3, which can accept a wide range of nucleophile

Nucleophile

A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

s to give the desired product 4.