2 1,2,3,4-Tetrahydro-P-carboline

Herraiz, T., Huang, Z., and Ough, C. S. (1993). l,2,3,4-Tetrahydro-P-carboline-3-carboxylic acid and 1-Methyl-1,2,3,4-tetrahydro-P-carboline-3-carboxylic acid in wines. ]. Agric. Food Chem. 41, 455—459. 

Pictet-Spengler cyclization. 1,2,3,4-Tetrahydro-P-carboline derivatives result from CAN oxidation of carbamates of N-trimethylsilylmethyltryptamine. 

Using the powerful structural elucidation technique of tandem mass spectrometry coupled with on-line HPLC (LC-ESI-MS/MS), the structural characterization of a number of additional contaminants of L-tryptophan associated with EMS has been performed.18 The identity of the contaminants were as follows. Peaks UV-5 included 3-phenylamino-L-alanine (PAA) l,l -ethylidenebis(tryptophan) (EBT) 2-(3-indolymethyl)-L-tryptophan (200) (all identified as case related). Peaks 1,3-carboxyl-1,2,3,4-tetrahydro-p-carboline 2,3-carboxy-l-methyl-l,2,3,4-tetrahydro-P-carboline 2-(2,3 dihy-droxy-l-[3-indolyl]-propyl)-L-tryptophan (100) and diastereomers of 3-car-boxy-l-[3-indolyl-methyl]-l,2,3,4 tetrahydro-P-carboline (300 and 400), were confirmed by this technique. Peak P31, previously unresolved from peak 200, a case-related compound, has been tentatively identified as 2-(3-indolyl)-L-tryptophan. Thus, progress on structural analyses of contaminants has progressed far beyond studies evaluating their toxicologic and physiologic potentials. 

Figure 16.1. Solid-phase synthesis of 1,2,3,4-tetrahydro-p-carbolines. (Reproduced from 26].)...

The factors that control diastereoselection in the construction of 1,3-disubstituted tetrahydro-p-car-bolines are not, as yet, well understood. With many aldehydes a slight preference for forming the trans diastereomer is observed. " This preference is somewhat greater when the indole nitrogen (Na) of the tryptamine is alkylated. Pictet-Spengler cyclizations of Nb-benzyltryptophan methyl ester under Cook s aprotic conditions are reported to provide nearly exclusively the rr 2ni-A b-benzyl-3-methoxycarbonyl-1 -substituted-1,2,3,4-tetrahydro-P-carbolines. ... 

In 1983 an approach for forming either enantiomer of a 1-alkyl-1,2,3,4-tetrahydro-p-carboline from l-(-)-tryptophan was published. Specifically, tryptophan was converted into derivatives (33) and (35) (Scheme 19). When the secondary amine (33) was condensed/cyclized with methyl 4-formyl-2,2-... 

Systematic structure activity relationships (SARs) around the scaffold of the natural alkaloid yohimbine led to the discovery of 1,2,3,4-tetrahydro-p-carboline (THpC) derivatives that have been shown to be very potent and highly selective 5HT2b receptor antagonists. Of particular interest are 1-substituted-THpC compounds (1 to 4) that were selected for further development (Figure 6.1). 

Tetrahydro-p-carbolines, important structural elements of many tryptophan-derived natural alkaloids, showed a broad spectrum of pharmacological activities. One-pot cyclocondensation of polymer-bound tryptophan 399 with different aldehydes and ketones in CHCI3 in the presence of/>-toluenesulfonic acid (PTSA) as catalyst were carried out under MWI to give polymer-bound 1,2,3,4-tetrahydro-p-carboline derivatives within 15 min. Subsequent reaction with KCN in MeOH at room temperature gave 400 in 87-96% yields (Scheme 80). When cyclization was carried out under reflux in CHCI3 for 15 min using identical stoichiometry, no... 

FIGURE 11.59 1,2,3,4-Tetrahydro-P-carboline-derived diketopiperazines library. (From Kundu, B., Solid-phase strategies for the design and synthesis of heterocyclic molecules of medicinal interest, Curr. Opin. Drug... 

Tryptophan-derived 1,2,3,4-tetrahydro-P-carboline and 3-carboline alkaloids result in foods through a Pictet-Spengler condensation (a special case of the Mannich reaction) of indoleamines, such as tryptophan and tryptamine, with aldehydes. The mechanism of the Pictet-Spengler reaction leading to... 

General Procedure for Synthesis of 1,2,3,4-Tetrahydro-P-carboline by Domino Copper-Catalyzed Three-Component Indole Formation and Cyclization with t-BuOK Synthesis of 2-Methyl-l-propyl-2,3,4,9-tetrahydro-lH-pyrido[3,4-hjindole (6a) and 2-Methyl-l-propyl-l,2,3,4-tetrahydropy-razino[l,2-a]indole (8a) (Table 1, Entry 11)... 

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