Piperine

Along with its isomer chavicine, piperine from black pepper and long pepper has pungency effects via activation of TRPV1. Piperine also inhibits CYP2J2.

It has been used in some forms of traditional medicine. It can be acutely toxic if swallowed in extremely high doses. (>300mg/kg)

Preparation

Extraction

Due to its poor solubility in water, piperine is typically extracted from black pepper by using organic solvents like dichloromethane or ethanol. The amount of piperine varies from 1–2% in long pepper, to 5–10% in commercial white and black peppers.

Piperine can also be prepared by treating the solvent-free residue from a concentrated alcoholic extract of black pepper with a solution of potassium hydroxide to remove resin (said to contain chavicine, an isomer of piperine). The solution is decanted from the insoluble residue and left to stand overnight in alcohol. During this period, the alkaloid slowly crystallizes from the solution.

Chemical synthesis

Piperine has been synthesized by the reaction of piperonoyl chloride with piperidine.

Biosynthesis

The biosynthesis of piperine is only partially known.

• The last step is catalyzed by piperine synthase (piperoyl-CoA:piperidine piperoyl transferase). As suggested by its systematic name, it converts piperoyl-CoA and piperidine into piperine.
• Piperoyl-CoA is made by piperoyl-CoA ligase from piperic acid, which is in turn made from feruperic acid by CYP719A37.
• Feruperic acid is presumably made from ferulic acid. Piperine is presumably made from lysine.

In addition to piperine synthase PipBAHD2, there is an orthologous enzyme with broader substract specificity in Piper nigrum with gene symbol PipBAHD1, called a "piperamide synthase". This other enzyme is responsible for the many piperamide compounds (see ) besides piperine found in black pepper. Both enzymes are BAHD acyltransferases.