Gramine and Its Derivatives

All the above results are consistent with Wenkert s recent suggestion (57a) that the biological conversion of tryptophan into gramine proceeds by condensation with pyridoxal phosphate (Ilia) with formation of a 

Schiff s base (Illb), which is then degraded by a reverse Michael reaction to the protonated 3-methyleneindolenine (IIIc). Addition of ammonia then yields 3-aminomethylindole, which on methylation affords gramine (III). This attractive hypothesis finds support in the recent isolation from barley seedlings of both 3-aminomethylindole and 3-methyl-aminomethylindole (57b). It is also supported by the demonstration that 3-aminomethylindole can be methylated to 3-methylaminomethylindole 

In retrospect, the report that phenylalanine is not a precursor of tryptophan and therefore of gramine in barley is not surprising it seems more probable that anthranilic acid is a precursor (57c). 

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Dimerization is also prevented by the presence of a formal positive charge on a j8-substituent, thus tryptamine cannot be dimerized. The formation of the trimer can be rationalized by analogy with the reactions of gramine and its derivatives. Thus, Thesing and Mayer found that methylphenylskatylamine (49) reacts with... 

Among the indole Mannich bases, the alkaloid gramine (3-dimethylaminomethylindole) and its derivatives have foimd the most extensive applications. They are valuable intermediate products in the synthesis of different important eompounds - heteroauxine, tryptophane, and the series of tryptamines. 

The photochemical reaction of tertiary amines with C6o can be used to synthesize alkaloid-C6o derivatives [269], Irradiation of alkaloids bearing a tertiary amino group such as tazettine, gramine, scandine, or 10-hydroxyscandine with C6o led to the isolation of alkaloid-C6o adducts. Use of tazettine and gramine in the reaction yielded the expected [6,6] adduct. In addition to the pyrrolidinofullerene 94a-b, a new type of monoadduct 95a-b with a bis-[6,6] closed structure characterized by UV-vis, FT-IR, II-NMR, 13C-NMR, II- II-COSY, ROESY, HMQC, and HMBC spectroscopy was obtained from the reaction with scandine 93a and its 10-hydroxy derivative 93b (Scheme 38). 

Aminomethylindoles are particularly important synthetic intermediates. 3-Dimethyl-aminomethylindole (gramine) (153) and especially its quaternary salts readily undergo displacement reactions with nucleophiles (Scheme 60). Indole-2,3-quinodimethanes, generated from 2-methylgramine as shown in Scheme 61, undergo intermolecular cycloaddition reactions with dienophiles to yield carbazole derivatives (82T2745). 

Methylgramine (356) generally reacts analogously to gramine, but with potassium cyanide it yields a mixture of the 2-cyano-3-methyl (357) (by S N reaction) and the 3-cyanomethyl derivatives. 

Gramine - 3-(dimethylaminomethyl)indole (14) - is a readily obtainable derivative of indole and is produced with a quantitative yield by the Mannich reaction. In [19] it was phosphorylated with diethyl chlorophosphite. 3-(Dimethylaminomethyl)-l-(triethoxyphosphito)indole (15) was obtained also by the method in [20] using diethyl penten-3-on-2-yl phosphite. Compound 15 readily adds sulfur with the formation of the corresponding gramine 1-thiophosphate 16 and reacts with chloral according to the scheme of the Perkow reaction, forming phosphate 17 ... 

Patrikeev et al. also employed imprinted silicas for thin layer chromatography. The silica was mixed with plaster and immobilised on a plate for use in the separation and identification of gramines [31] and for the resolution of amino acid derivatives [29]. In the latter experiment it was found that the influence of the amino acid protective group, dinitrophenol, was too dominant to allow the separation of... 

Table I is a compilation of plant species which contain the simple indole alkaloid types of Fig. 1. As mentioned earlier, the main requirement for the inclusion of a certain simple indole alkaloid into Table I is that it contain a tryptamine unit as a readily distinguishable feature in its structure. That tryptamine is a precursor in the biosynthesis of many of the b, c, d, and e type simple indole bases is yet to be shown although it is felt that future work will prove the correctness of such a view. Gramine, the simplest indole alkaloid, has been included in the tryptamine classification a because it is biosynthetically related to tryptophan cryptole-pine has been likewise included therein although its structural relationship to tryptophan appears more obscure (Volume VIII, Chapter 1, pp. 4, 19). The calycanthine type does not possess a tryptamine structure but it is included in the simple indole alkaloid b classification since most of its congeners are tryptamine derivatives and since it exhibits a close biogenetic relationship to this latter (chimonanthine) type (Volume VIII, Chapter 16). Type d is represented by the small number of the so-called canthin-6-one alkaloids (Volume VIII, pp. 260-252, 497-498). The most recent variation of the simple indole alkaloids is found in the Anacardiaceae family. Its indoloquinolizidine nucleus suggests inclusion with type d on the basis of structural and biogenetic similarity. Finally, simple indole alkaloid type e is composed of the well-defined evodiamine (rutaecarpine) structural form (Volume VIII, Chapter 4).

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