Synthetic Applications of the Nenitzescu Reaction to Biologically Active 5-Hydroxyindoles

A variety of natural and unnatural molecules containing a 5-hydroxyindole moiety have displayed strong pharmacological activities. In this context the Nenitzescu reaction has proven to be extremely useful for the preparation of 5- hydroxyindoles directly from simple and accessible materials like 1,4-benzoquinone and enamines. This review will summarize recent applications for the synthesis of complex 5-hydroxyindole derivatives such as pyrimido[4,5-b]indol-4- amines, 5H-benzo[b]carbazoles, 5'-hydroxynaltrindolomorphinans, and 3-[3-(amidomethyl)-2-ethyl-1-(phenylmethyl)- 1H-indol-5-yloxy]propylphosphonic acid (LY311727) which possess important biological activities. The Mechanism of the Nenitzescu reaction is discussed and as is recent utilization of solid phase chemistry to the Nenitzescu reaction.