Tryptophan Mannich reaction

The second line of circumstantial evidence quoted in support of this hypothesis is the ready formation of l,2,3,4-tetrahydro-/3-carboline derivatives under pseudo-physiological conditions of temperature, pH, and concentration. Tryptamine and aldehydes, trypt-amine and a-keto acids, and tryptophan and aldehydes condense at room temperature in a Pictet-Spengler type intramolecular Mannich reaction in the pH range 5.2-8.0 (cf. Section III, A, 1, a). It was argued that experiments of this type serve as models for biochemical reactions and may be used in evidence. 

Sato, A., Nozoe, S., Toda, T., Seio, S., and Nozoc, T., Application of the Mannich reaction to l-azaazulan-2-one. Syntheses of seven-membered analogues of tryptophan and related compounds. Bulk Chem. Soc. Jpn., 46, 3530. 197.3. 

Also, a large number of indole alkaloids are formed by Mannich reactions involving tryptophan or its decarboxylation product tryptamine with various aldehydes. Both the a- and p-position of the indole nucleus are electronegative, and a Mannich reaction with tryptamine can yield a p-carboline derivative or a 3,3-spiroindolenine [30]. A further example is provided by the tropinone biosynthesis (Figure 1.29) [31 ]. 

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... 

Biosynthesis of some classes of terpene indole alkaloids is well understood. In certain cases, many of the enzymes that are responsible for biosynthesis have been cloned and mechanistically studied. In other cases, biosynthesis pathway is only proposed based on the results of feeding studies with isotopically labeled substtates and from the structures of isolated biosynthetic intermediates. All terpene indole alkaloids are derived from tryptophan and the iridoid terpene secologanin (Fig. 14.11). Tryptophan decarboxylase, a pyridoxal-dependent enzyme [29], converts tryptophan to tryptamine [30]. The following strictosidine synthase-catalyzed Mannich reaction connects ttyptamine and secologanin to yield strictosidine [31]. The Apocynaceae, Loganiaceae, Rubiaceae, and Nyssaceae families of plants each produce terpene indole alkaloids with dramatically diverse structures [32-34]. The mechanisms and control of... 

The Mannich reaction is an excellent method for the synthesis of P-amino carbonyl compounds and their derivatives, and unmodified primary amino acids were found to be enormously useful for this important reaction. Cdrdova et al. [42] reported the first primary amino acid-promoted three-component Mannich reaction of ketone, p-anisidine, and aldehydes primary amino acids, such as L-alanine and L-vahne, were excellent catalysts and led to the formation of Mannich products with up to >99% ee. Barbas and coworkers [31] also showed L-tryptophan catalyzed the direct threeMannich reaction of hydroxyacetone, p-anisidine, and aromatic aldehydes good yields, high diastereoselectivity, and excellent ee were attainable. 

Although the number of successful applications of primary amino acids in stereoselective organocatalysis is far fewer than for the secondary amine, a few interesting examples are worth pointing out. The diversity of primary amino acids in aldol and Mannich reactions has been reviewed recently [48]. Several primary amino acids, such as alanine, valine, tryptophan, and threonine have been used as orga-nocatalysts. For instance, Barbas and coworkers have demonstrated the use of a L-threonine catalyzed protocol towards the synthesis of syn-l,2-diols through direct aldol reaction between a-hydroxyketones and para-nitrobenzaldehyde (Figure 17.13) [49]. 

Bischler-Napieralski reactions, 4, 279 carboline synthesis from, 4, 516 Mannich-type reactions, 4, 279 sulfur isosteres, biological activity, 4, 913 synthesis, 4, 337, 913 Tryptophan biosynthesis, 1, 264 carboline synthesis from, 4, 516 molecular structure, 4, 162 Tryptophan hydroxylase in serotonin biosynthesis, 1, 261 Tryptophan oxygenase... 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

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