The pictet‐spengler reaction and biogenic tryptamines: Formation of tetrahydro‐β‐carbolines at physiological pH

Biogenic tryptamines 1a‐c were reacted with aldehydes 2a & b and α‐keto acids 2c & d to form 1,2,3,4‐tetrahydro‐β‐carbolines (THBCs) 4d‐1 , and other products, in a buffered solution at 37° and p H 7.4. These reactions were followed over time by 1 H nmr through integral changes in discrete signals in the spectra. Reactions between tryptamines and acetaldchyde ( 2b ) gave the expected 1‐methyl‐THBCs 4d‐f , while those with sodium glyoxylate ( 2c ) resulted in THBC‐1‐carboxylic acids 4g‐1 . Surprisingly, reactions with sodium pyruvate ( 2d ) or formaldehyde ( 2a ) did not form the expected products 4a‐c or 4j‐1 , respectively under these conditions. In successful reactions, 5‐methoxytryptamine ( 1c ) was found to be more reactive than tryptamine ( 1a ) or serotonin ( 1b ). MOPAC calculations were employed to investigate reaction intermediates. These results are applicable in research related to aberrant tryptamine metabolism; e.g. depression and alcoholism.