Betanidin reactions

Figure 2.23 Biosynthesis of betalains, involving two early enzymes, the tyrosinase (1A, hydroxylating activity 1 B, oxidizing activity) and the Dopa 4,5-dioxygenase (2), and one late enzyme activity, glucosylating cyc/o-Dopa and/or betanidin (3). Reactions 4 and 5 are considered to proceed spontaneously.

On treatment of 11 with palladium, an interesting disproportionation reaction takes place which yields the colorless indole derivative 14 (27,28). Reaction of betanidin with acetyl chloride in trifluoroacetic acid afforded di-C>-acetyl-betanidin (13), which could be hydrolyzed back to 1 with concentrated hydrochloric acid (5). This demonstrated the presence of two phenolic hydroxyl groups in betanidin, and from consideration of the H-NMR data formula 1 was assigned to betanidin. 

The (25) configuration of betanidin has been determined by the identification of degradation product 7 as (5)-cyclodopa (5). For the determination of the absolute configuration at C-15, studies on the stereochemical relationship of betanidin (1) and isobetanidin (6) were of importance. It was found that on hydrolysis of betanin (5) under drastic conditions (18% HCl, 87°C) the ratio of 6 to 1 formed increased with the reaction time, whereas with concentrated HCl at room temperature the aglycone contained only 5% of 6 (29). On treatment of either pure 1 or 6 with 0.4 N KOH at 25°C with exclusion of oxygen, a 1 2 equilibrium mixture of the two isomers was formed. That the epimerization takes place at C-15 is indicated by the fact that both isomers gave the same optically... 

Betanidin hydrochloride is smoothly decarboxylated in boiling ethanol (33). In order to investigate the mechanism of this reaction, the decarboxylation of 1 was performed in monodeuterioethanol (34). The resulting decarboxybetanidin (19),... 

The betalamic acid derivatives obtained by total synthesis have been used for the preparation of natural and unnatural betalains following the procedures developed for amino acid exchange described earlier (Scheme 4). Reaction of the 9 1 ElZ mixture of semicarbazone 66 with the p-toluenesulfonate salt of (S)-cyclodopa methyl ester in dilute methanolic HCl afforded betanidin trimethyl ester (9), which was hydrolyzed with aqueous HCl to yield a 4 6 mixture of betanidin and isobetanidin 91). In the case of L-proline, the reaction had to be carried out in dilute aqueous ammonia because of the sensitivity of the resulting indicaxanthin (2) toward acids. Most likely, an inseparable mixture of 2 and its C-13 epimer T was obtained under these conditions. 

A number of betanidin analogues have been prepared by reaction of the methyl ester of cyclodopa 84 with suitably functionalized imine salts (75C527) (85HCA1670) (86HCA1588). A typical transformation is shown in Eq. (7) (75C527). 

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