The benzo-2-pyrone nucleus of the simple coumarins derives from the phenylacrylic skeleton of cinnamic acids.

The coumarin structure is derived from cinnamic acid via ortho-hydroxylation (a), trans-cis isomerisation of the side chain double bond (b) and (c), and lactonisation (d). The trans form is stable and could not cyclise, therefore, there should be isomerisation of some sort and the enzyme isomerase is implicated.

Coumarins are present in GRASSES.

The cis form is very unstable, therefore, will tend to go to the trans configuration. Glucose is a good leaving group which assists in the cis-trans transformation. A specific enzyme found in Melilotus alba (Leguminosae) specifically hydrolyses the cis-glucoside (beta-glucosidase).

This biosynthesis pathway should be followed by all coumarins oxygenated at position 7.

Umbelliferone, esculetin and scopoletin are the most widespread coumarins in nature.

During the synthesis of these compounds ortho-hydroxylation should respectively take place on p-coumaric, caffeic and ferulic acid.

TO BE CONTINUED

FRIEDLI ENTERPRISES
Georges-Louis Friedli, PgDip., MSc., PhD.
georges-louis@friedli.com