3,6-Dihydronicotinic acid

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 manner in which the two nicotinic acid units may be joined (Scheme 1) is suggested by analogy with the probable intermediacy of a dihydronicotinic acid in nicotine biosynthesis. It is further suggested that anatalline (4) and nicotelline (5) are trimers of the dihydro-derivative (7). ... 

When a drug is covalently coupled to 1-methyl-1,4-dihydronicotinic acid through an enzymatically labile... 

A nicotinic acid decarboxylase has been isolated from the roots of N. rustica. The pyrroline (141) is a nicotine precursor and gives nicotine, it has been suggested, by condensation with the dihydronicotinic acid (140), Scheme 17. 

In the tobacco plant, the nicotinic acid is reduced first, and a nucleophilic attack of deprotonated dihydronicotinic acid on the l-methyl-3,4-dihydropyrrolium salt gives (-)-nicotine. [536]... 

On the other hand, when [6- H]nicotinic acid was fed to the above system, the total amount of was considerably decreased compared with the result when [2— H], [4- H], or [5- H]nicotinic acid was used as a precursor. This supports the idea that 3,6-dihydronicotinic acid exists as an intermediate in the biosynthetic pathway. The stage at which decarboxylation occurs has not been finally clarified, but it seems that it is in concert with the condensation reaction of 3,6-dihydronicotinic acid with A -pyrroHdine or A -piperidine, because the label from [2— C]nicotinic acid remains at the C-2 of nicotine and is not randomized between C-2 and C-6 through the involvement of a symmetrical intermediate. 

The biosynthesis of the piperidine-type nicotinoid anabasine proceeds in an analogous manner to nicotine, with A -piperideine (instead of the A-methyl-A -pyrrolinium cation) as the counterpart of nicotinic acid/3,6-dihydronicotinic acid (Leete 1969). Consequently, L-lysine is the source of the piperidine ring instead of L-omithine (Solt et al. 1960). Unlike the conversion of the latter to the N-methyl-A -pyrrolinium cation via free putrescine, the conversion of lysine to A -piperideine is assumed to proceed via a bound cadaverine (Friesen et al. 1992). 

The photochemical cycloaddition of vinylogous formamides to olefins affords 1,4-dihydronicotinic acid derivatives in almost quantitative yield (Scheme 88). ... 

Niaotiana tabaom. - Saunders and Bush ° have attempted to relate the relative amounts of nicotine (84) and nornicotine (85) found in different genotypes of Niaotiana tabaom with the levels of the enzymes putrescine JV-methyltransferase (PMT)and il -methyl-putrescine oxidase (MPO) in these different varieties, It is well established that nicotine is formed in tobacco by the route illustrated in Scheme 9 .Putrescine is methylated to yield iV-meth-ylputrescine, which is oxidized to 4-methylaminobutanal. Spontaneous cyclization affords the iy-methyl-A -pyrrolinium salt, which reacts with an activated form of nicotinic acid (probably 3,6-dihydronicotinic acid) to ultimately yield nicotine. Nornicotine... 

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