ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The total synthesis of a neobetanidine derivative (3b) is described.Preliminary experiments led to the synthesis of neobetenamine (4), which presents the ring system of neobetanidine (3). A general method for the synthesis of several compounds containing the essential neobetanidine chromophore (a 1, 7-diazaheptamethine system incorporating a pyridine ring) consisted of Vilsmeier-Haack condensations involving the active (enolizable) methyl group of γ-picoline. Neobetenamine (4) resulted from this reaction with N-formyl-indoline, and also by an amine exchange between indoline and the Vilsmeier-Haack product from γ-picoline and N-methyl-formanilide.The methyl group of γ-picoline-2, 6-dicarboxylic ester 9, however, was resistant to the Vilsmeier-Haack condensation, but could be activated by introduction of a carboxyl into it: 4-chloropyridine-2, 6-dicarboxylic ester (11a) (from chelidamic ester) was used to alkylate malonic ester. The product (12a) lost only one carboxyl group when saponified. The resulting 2, 6-dicarboxy-pyridine-4-acetic acid (13a) readily underwent a novel decarboxylative condensation with the Meerwein acetal of dimethyl formamide to 4-(2-dimethylamino-vinyl)-2, 6-dimethoxycarbonyl-pyridine (14b), the first synthetic derivative of a neobetalaine. The enamine 14b was subjected to amine exchange reactions with indoline to 2-decarboxy-5, 6-dideoxy-neobetanidine dimethyl ester (15), and with (S)-cyclodopa (16) 5, 6-di-O-methyl-neobetanidine trimethyl ester (3b). The latter was identical with the diazomethane transformation product of betanidine (1), the aglucone of the pigment of the red beet, betanine.A few proton resonance and electron spectral properties, as well as the basicities of several of the synthesized compounds, are tabulated and discussed as far as they express special structural and electronic features of the common 1, 7-diazaheptamethine chromophore.
Additional Material:
4 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19700530224
