Reaction of Tryptophan with Carbohydrates:  Mechanistic Studies on the Formation of Carbohydrate-Derivedβ-Carbolines

Abstract

Numerous carbohydrate-derived beta-carbolines have been identified for the first time in model reactions of tryptophan with glucose and ribose, as well as in food samples. Extending these structural studies, we performed detailed investigations to elucidate the corresponding intermediates and formation pathway of these alkaloids. Degradation experiments with purified tryptophan glycoconjugates established that only glyco-tetrahydro-beta-carboline-3-carboxylic acids, and not the N-glycosides nor the C-glycoconjugates represented the direct precursors of carbohydrate-derived beta-carbolines. In addition, the significance of the oxidative decarboxylation reaction as the initial step for formation of 1-substituted beta-carbolines was proven. Finally, the stereochemistry of the carbohydrate-derived side chain was studied by means of CD spectroscopy and HPLC-CD experiments. These detailed stereochemical analyses yielded experimental evidence for the racemization steps required for formation of the carbohydrate-derived harman alkaloids and confirmed the proposed reaction pathway.

The intermolecular Pictet-Spengler condensation with chiral carbonyl derivatives in the stereoselective syntheses of optically-active isoquinoline and indole alkaloids

“…42 According to Wang, the formation of compounds 14 and 15 from tryptophan and xylose, involves a sequence including Pictet-Spengler condensation, oxidative decarboxylation, tautomerization, and dehydrogenation steps, a mechanism in which isomerization of the sugarderived side chain at C-1' is essential. The use of glucose as model sugar allowed confirmation of the side chain isomerization feature.…”

“…A special class of isoquinoline alkaloids, which includes the widely known emetine from Cephaelis ipecacuanha can be formed by with dopamine (42) and related compounds.…”

“…139 Szabó and coworkers 140 studied the reaction of dopamine (42) and N-benzyldopamine (162) with tetraacetyl loganin (154a) and found that reaction with the natural product gave preferably the H-1α isoquinolines 161c,d, while the N-benzyl derivative 162 provided preferentially the H-1β heterocycles 161e,f. In both cases, the 7,8-disubstituted THIQ ("neo", 161d and 161f) were formed.…”

Effect of reaction conditions on product distribution from the co-pyrolysis of α-amino acids with glucose

“…Due to their importance to the food industry, the interaction of amino acids and sugars has been studied extensively [4][5][6][7][8][9]. Many of these studies focused on conditions that favor or reduce browning reactions [10,11], while others focused on the formation of specific products and the underlying reaction mechanisms [4,12].…”

Cytotoxic alkaloids from the marine shellfish-associated fungus Aspergillus sp. XBB-4 induced by an amino acid-directed strategy

“…22 Many researches demonstrated that the enzymatic Pictet-Spengler reaction, catalyzed by Pictet-Spenglerase, was one of the characteristics of b-carboline alkaloid biosynthesis. [23][24][25] Feeding experiments with 5-F-Trp and 13 C labeled glucose and acetate revealed that the synthesis of b-carboline involved a Pictet-Spengler cyclization, a decarboxylation and C-ring oxidation process. 26,27 Combining of the published literatures and basic organic synthesis mechanism, the biosynthetic pathway of compounds 1-3 were proposed.…”