Approaches to the synthesis of specifically substituted pyrido[4,3-b]indoles

ORGN 626

Wayne M. Stalick, wstalick@gmu.edu, Department of Chemistry and Physics, Central Missouri State Universitry, Warrensburg, MO 64093 and James H. Wynne, jwynne@ccs.nrl.navy.mil, Chemistry Division, Naval Research Laboratory, 4555 Overlook AVE, SW, Washington, DC 20375.
A number of reports have shown that γ-carbolines [4,3-b] indoles are of interest due to their biological activities. Interestingly, there seemed to be no generally applied synthetic pathways published which allowed for the introduction of functional groups in specific positions of the γ-carboline system. Our approach follows two pathways, first was a synthesis that used N-tosylaldimines as an integral step. The desired products were afforded but the yields were lower than expected. A newer approach significantly reduces the number of steps. The sequence begins with the acylation of indole in the 3-position, a reaction accomplished without the use of a protecting group. Subsequent reductive amination of the acylated product with amino acids affords a side chain that easily cyclizes to yield the γ-carboline nucleus. This approach allows for substituents to be placed in either the 1, 3, or 4 positions, or any combination of these, within the ring system.