Methyl-1-pyrrolinium cation

Sun J, MacFarlane D R, Forsyth M. A new family of ionic liquids based on the l-alkyl-2-methyl pyrrolinium cation. Electrochim. Acta. 

Condensation of the iV-methyl-zl -pyrrolinium cation with acetoacetate or acetoacetyl CoA, built from two molecules of acetyl CoA (D 3.1) obviously yields hygrine- x-carboxylic acid, a precursor of tropine and ecgonine. Hygrine may also be transformed to cuscohygrine. In the synthesis of this compound it reacts with a second molecule of the iV-methyl-/ -pyrrolinium cation. 

Fig. 5 Biosynthetic pathway of nicotine. Unbroken arrows indicate single enzymatic conversions and broken arrows indicate multiple enzymatic conversions. It is not known whether the 7V-methyl-pyrrolinium cation is coupled to nicotinic acid or a derivative of the latter. PMT putrescine A -methyltransferase...

L-metilionine to -adenosylmethionine. In this process a positively charged sulphur is produced and facilitates the nucleophilic reaction. By the activity of diamine oxidase, the A -methyl-A -pyrrolinium cation is formed and after that the first alkaloid, hygrine. From hygrine, by way of acetyl CoA, hydrolysis and intramolecular Mannich reactions, other pyrrolidine and tropane alkaloids are synthesized cuscohygrine, hyoscyamine or tropinone, tropine and cocaine. The Mannich reaction involves the combination of an amine, an aldehyde or a ketone with a nucleophilic carbon. This reaction is typical in alkaloid synthesis, and can be written as follows ... 

In the case of non-protein amino acid-derived alkaloids, the second obligatory intermedia is derived from the obligatory intermedia enzymatically and by the Schiff base formation as, for example, in the hygrine pathway. The second obligatory intermedia is, in this case, the A-methyl-A pyrrolinium cation. 

Pyrrolidine alkaloids have a pyrrolidine (C4N skeleton) nucleus. The structural a of these alkaloids is L-ornithine (in plants) and L-arginine (in animals). The pyrro-line skeleton is synthesized after /3 (putrescine) and

Schiff base reaction forms which is A-methyl-A -pyrrolinium cation. Subsequently, A (hygrine) is formed. Typical pyrroline alkaloids are (-)- and (-1-)- hygrines (Figure 56). 

The structure of cuscohygrine arises by an intermolecular Mannich reaction involving a second /V-methyl-A1 -pyrrolinium cation (Figure 6.3). 

In the formation of nicotine, a pyrrolidine ring derived from ornithine, most likely as the /V-methyl-A1 -pyrrolinium cation (see Figure 6.2) is attached to the pyridine ring of nicotinic acid, displacing the carboxyl during the sequence (Figure 6.31). A dihydronicotinic acid intermediate is likely to be involved allowing decarboxylation to the enamine 1,2-dihydropyridine. 

The V-methyl -A1 -pyrrol ini um cation is the last common intermediate in both TA and nicotine biosynthesis (Fig.7.4). V-Methy 1-A1 -pyrrolinium cation formation begins with the decarboxylation of ornithine and arginine by ornithine decarboxylase (ODC) and arginine decarboxylase (ADC), respectively. Putrescine is formed... 

The first committed step in TA and nicotine biosynthesis is catalyzed by putrescine JV-methyltransferase (PMT) (Fig.7.4).82 A PMT cDNA isolated from tobacco showed extensive homology to spermidine synthase from mammalian and bacterial sources.83 A-Methylputrescine is oxidatively deaminated to 4-aminobutanal, which undergoes spontaneous cyclization to form the reactive A-methyl-A1-pyrrolinium cation. Although the enzymes involved are unknown, the A-methyl-A1-pyrrolinium cation is thought to condense either with acetoacetic acid to yield hygrine as a precursor to the tropane ring, or with nicotinic acid to form nicotine. 

The subsequent reactions leading from 7V-methylpyrrolinium to tropinone remain doubtful since no enzymes have yet been demonstrated. For a long time, it was believed that the formation of the tropane ring from the jV-methyl-A -pyrrolinium cation occurred by condensation with an acetoacetyl unit, with the release of CO2, to form hygrine. This was... 

A further intramolecular SB by condensation of 4-(methylamino)butanal leads to the A-methyl-A -pyrrolinium cation, which is the precursor of cocaine biosynthesis (Figure 1.28) [26, 27]. 

Figure 1.28 Examples of Schiff base condensations, (a) Dialdehyde amine (precursor of the pyrrolizidine ring system), (b) piperidine-2-carboxylic acid (a precursor of anabasine), and (c) iV-methyl-A -pyrrolinium cation (precursor of cocaine).

The first product of the cyclization, A -methyl-A -pyrrol-ideine (or the N-methyl-A -pyrrolinium cation) (3), has been... 

Tropane alkaloids result from addition of acetate/malonate to a precursor such as the 1-methyl-A pyrrolinium cation (3), followed by intramolecular cycliza-tion (Leete, 1990) (Figs. 29.2 and 29.6). (/ )-Hygrine (4) in several plants, primarily those of the Solanaceae and Eryth-roxylaceae, may react intramolecularly to form tropane alkaloids (Fig. 29.6). Pyrrolidine alkaloids, such as (/ )-hygrine (4) and cuscohygiine (5), frequently co-occur with tropane alkaloids. 

The reaction of pipeiideine precursors, homologous to the A -methyl-A -pyrrolinium cation (3) involved in tropane alkaloid formation, with acetyl-CoA or malonyl-CoA can... 

Further step in the pathway is reaction catalyzed by the diamine oxidase enzyme, Ai-methylputrescine oxidase (MPO EC 1.4.3.6). This enzyme leads to oxidatively deamination of Ai-methylputrescine 13 to 4-(methylamino)butanal 14, which after spontaneous cyclization forms the reactive precursor of the tropane nucleus -7/-methyl-A -pyrrolinium cation 20 [2, 7, 36]. This enzyme requires copper as a cofactor and belongs to a class of amine oxidases. cDNA was isolated from tobacco [37]. This enzyme has been isolated by root cultures of H. niger L.,... 

Tropane alkaloids are found mainly in the Solanaceae [14] plant family. First biosynthetic step of tropane alkaloids starts with iV-methylation of putrescine (derived from L-omithine) to form Al-methylputrescine. After the conversion to 1-methyl-Al pyrrolinium cation, its condensation with nicotinic acid gives rise to nicotine synthesis, while other chemical conversions lead to the formation of tropinone, the precursor of many tropane alkaloids through branched pathways (Fig. 8.8a) [15]. 

Precursor in the biosynthesis of tropane alkaloids is the amino acid L-omithine (1) [5-8]. It was found that ornithine undergoes enzymatic decarboxylation to putrescine (2) which then is methylated to A-methylputrescine (3) [9-12]. The oxidation of iV-methylputrescine (3) leads to 4-methylaminobutanal (4) that is further converted in the M-methyl-A -pyrrolinium cation (5). From the last compound, the four carbon atoms C-1, C-5, C-6, and C-7 and A-methyl group in tropane skeleton are originated [9, 13, 14] (Scheme 12.1). 

The next steps of formation of the tropane skeleton require addition of two acetate units to iV-methyl-A -pyrrolinium cation (5) to obtain tropinone (6) - dominating pathway for alkaloids in plants belonging to family Solanaceae [15, 16] and ecgoninone (7) dominating pathway for alkaloids in plants belonging to family Erythroxylaceae [11, 17, 18]. On the other hand, biogeneticaUy tropinone (6) is... 

The next step, the methylation of putrescine, already belongs to the secondary metabolism and is catalyzed by the first pathway-specific enzyme, putrescine A-methyltransferase (PMT) discovered in tobacco roots (Mizusaki et al. 1971). Its product, A-methylputrescine, represents the direct precursor of 4-methyl-aminobutanal, as was shown by a cell free preparation of tobacco roots. The oxidative deamination of the diamine is catalyzed by A-methylputrescine oxidase, an enzyme of ahigh substrate specificity (Mizusaki etal. 1972). 4-Methy laminobutanal is cyclized spontaneously forming the A-methyl-A -pyrrolinium cation (present as a salt) (Leete 1967). An alternative route has been proposed for the biosynthesis... 

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