Jc. Callaway et al., THE PICTET-SPENGLER REACTION AND BIOGENIC TRYPTAMINES - FORMATION OF TETRAHYDRO-BETA-CARBOLINES AT PHYSIOLOGICAL PH, Journal of heterocyclic chemistry, 31(2), 1994, pp. 431-435
Biogenic tryptamines 1a-c were reacted with aldehydes 2a & b and alpha
-keto acids 2c & d to form 1,2,3,4-tetrahydro-beta-carbolines (THBCs)
4d-i, and other products, in a buffered solution at 37-degrees and pH
7.4. These reactions were followed over time by H-1 nmr through integr
al changes in discrete signals in the spectra. Reactions between trypt
amines and acetaldehyde (2b) gave the expected 1-methyl-THBCs 4d-f, wh
ile those with sodium glyoxylate (2c) resulted in THBC-1-carboxylic ac
ids 4g-i. Surprisingly, reactions with sodium pyruvate (2d) or formald
ehyde (2a) did not form the expected products 4a-c or 4j-1, respective
ly under these conditions. In successful reactions, 5-methoxytryptamin
e (1c) was found to be more reactive than tryptamine (1a) or serotonin
(1b). MOPAC calculations were employed to investigate reaction interm
ediates. These results are applicable in research related to aberrant
tryptamine metabolism; e.g. depression and alcoholism.