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

Abstract 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 pH 7.4. These reactions were followed over time by 1H 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.