Examples of Notable Indole Syntheses

Ondansetron is a selective, 5-hydroxytryptamine antagonist, nsed to prevent vomiting dnring cancer chemotherapy and radiotherapy. 

Staurosporine and related molecules are under active investigation as potential anti-tumour agents. The synthesis illustrates several aspects of heterocyclic chemistry, including a 2-pyrone acting as a diene in an intramolecular Diels-Alder reaction, and the use of nitrene insertion for the formation of 5-membered nitrogen rings. 

Serotonin has been synthesised by several routes the method shown relies on a Fischer indole synthesis, the requisite aryl-hydrazone being constructed by a process known as the Japp-Klingemann reaction in which the enol of a 1,3-dicarbonyl compound is reacted with an aryl-diazonium salt, with subsequent cleavage of the 1,3-dicarbonyl unit. 

This synthesis uses the approach of starting from a pyrrole the cyclic ketone intermediate is in general a useful intermediate for the synthesis of 4-substituted indoles - in this case a sulfur substituent - it is already at the aromatic oxidation level needing only the loss of the 4-chlorophenylthiol. 

---