SYNTHESIS OF THE ENANTIOMERS OF SUBSTITUTED ALPHA-METHYLTRYPTAMINES AS SEROTONIN RECEPTOR PROBES
Abstract
A brief review of serotonin pharmacology in the central nervous system is presented. The pharmacology of alpha-methyltryptamines is discussed, and the rationale for the design of certain analogs as chiral serotonin receptor probes is explained. A synthetic/chromatographic sequence was developed to provide a general route to aromatic-ring-substituted alpha-methyltryptamines. Specifically, the 4-hydroxy, 5-hydroxy, 4-methoxy, and 5-methoxy isomers were primary synthetic targets. The key step was a reductive amination of substituted indole-2-propanones with the pure enantiomers of alpha-methylbenzyl amine, followed by separation of the resulting diastereomeric amines using preparative centrifugal chromatography. N-debenzylation provided the target compounds in high optical purity. Improved procedures for the preparation of substituted indoles and indolepropanones were also developed.
Degree
Ph.D.
Subject Area
Organic chemistry
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.