Tryptamine intramolecular Mannich reaction

One instance of an intramolecular Mannich reaction of an A -acyl-tryptamine has been reported. ... 

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. 

One of the less elaborated indole alkaloid structural variations is typified by ebumamonine (78). A combined chemical and enzymatic route for its synthesis is shown in Scheme 6 (1994T9487, 1990JOC517). Condensation of the enantiopure aldehyde 76 with tryptamine in a classical intramolecular Mannich reaction, with concomitant lactam closure, produced the tetra-cycle 77. 

Conducted in an intramolecular sense, Mannich reactions have been much used for the construction of tetrahydro-P-carbolines. ° Tryptamines carrying a 2-carboxylic acid group, which can be conveniently prepared (20.16.6.3), but are not easily decarboxylated as such, undergo cyclising Mannich condensation with aldehydes and ketones, with loss of the carbon dioxide in a final step. ° ... 

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