Trigonelline

The conversion of proline to stachydrine was based on experiments with Stachys palustris L., S. recta L., and Galeopsis ochrolev a Lam. (108). 

Trier (101) extended his hypothetical suggestions to the formation of nicotine, again taking proline as the amino acid starting point. The only other reactant postulated was formaldehyde, which was supposed to give rise by Cannizzaro reaction to formic acid and methyl alcohol. Proline was supposed to be methylated by the alcohol, and reaction of a second proline molecule with formic acid was presumed to provide nicotinic acid. Nicotinic acid and methylproline were presumed to give nicotine and COi by oxidation. 

The feeding experiments of Ciamician and Ravenna (109) can now be considered as of merely historical interest on account of the crudities of their technique and the substances investigated. The only concrete result seems to have been to show that the wounding of tobacco plants might in itself lead to considerable formation of nicotine. Trier s speculations may therefore be considered to have afforded a starting point for subsequent experiments which have been concerned with the effect of proline and related substances. 

More satisfactory experiments have been carried out by Dawson (112). He raised tobacco plants of commercial varieties and selected groups for 

NICOTINE FORMATION IN LEAVES OF TOBACCO (112) MILLIGRAMS OF NICOTINE PER PLANT. 

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About 50—80% of the trigonelline is decomposed during roasting. Trigonelline is a probable source for niacin [59-67-6] but also a source of some of the aromatic nitrogen compounds such as pyridines, pyrroles, and bicycHc compounds found in coffee aroma (16). Certain acids, such as acetic, formic. 

Trigonelline (1-methylnicotinic acid zwitterion) [535-83-1] M 137,1, m 218°(dec). Crystd (as monohydrate) from aqueous EtOH, then dried at 100°. 

When trigonelline is heated in closed tubes with baryta water at 120°, it gives rise to methylamine, whilst similar treatment with hydrochloric acid at 260° furnishes methyl chloride and nicotinic acid (pyridine-3-carboxylic acid), indicating that it is the methylbetaine of nicotinic acid. 

Hantzsch prepared this betaine by treating nicotinic acid methiodide with silver hydroxide and. lahns subsequently identified trigonelline with Hantzsch s synthetic base. 

Trigonelline appears to exert no marked physiological action. Ackermann first observed that nicotinic acid administered to dogs appears in the urine as trigonelline. 

Astragalus spp. Members of this genus are included in the group of loco weeds causing disease in cattle in the United States. From A. carlei. Pease and Elderfield isolated a- and j3- earleines, which were later shown by Stempel and Elderfield to be betaine and choline respectively these are also present in A. wootoni, along with trigonelline (p. 7). ( (1) J. Org. Chem., 1940, 5, 192, see also p. 198 (2) Ibid., 1942, 7, 432 J. Amer. Chem. Soc., 1941, 63, 315. (3) Knowles and Elderfield, J. Org. Chem., 1942, 7, 389). 

Pyridine is formed from trigonelline during roasting.3 It is presumed to contribute to the flavor, especially in the darker coffee roasts.15... 

Trigonelline is present in green coffee (1 %),15 but it is rapidly decomposed on roasting so that only about 0.1% trigonelline is present in a deeply roasted coffee.161 The products of trigonelline breakdown are evident in roasted coffee and include nicotinic acid and its methylester, pyridine, and p-picoline (Figure 17).3... 

Determinations of nicotinamide in green and roasted Robusta coffee are indicative of its much increased content in coffee roasted at or below 240°C. The values are 3 and 46 mg/100 g for green and roasted coffee, respectively.183 At least part of this increase is from trigonelline as it decomposes on roasting. 

The products from trigonelline seen in roasted coffee.3... 

Robusta coffee has undesirable flavor agents that can be masked by the addition of L-aspartyl-L-phenylalaninemethyl ester.218 The methylxanthine stimulant properties of coffee can be antagonized by spraying freshly roasted coffee beans with nicotinamide and nicotinic acid,219 quinolinic acid, or trigonelline.220... 

Viani, R., Horman, I., Determination of trigonelline in coffee, Coll. Int. Chim. Cafes 7, 273, 1975. (CA85 190824x)... 

Corria, D., Existence of trigonelline in yerba mate, Arq Biol Tecnol Inst Biol Pesquisas Tecnol, 2, 265, 1947. 

Saldana MDA. 1997. Extraction of caffeine, trigonelline and chlorogenic acid from Brazilian coffee beans using supercritical CO2 MSc. Thesis, UNICAMP, Campinas, Brazil. 

Fig. 8.14. Stepwise activation of dihydrotrigonelline-based chemical delivery systems, first by oxidation to a pyridinium cation (Reaction a), and then by hydrolysis to trigonelline and the drug ROH (Reaction b). Direct hydrolysis (Reaction c) is slow in comparison to the Reactions...

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