Ricininic acid

Ricinine forms a compound with mercuric chloride, C8Hs02N2HgCl2, m.p. 204°. It also gives a chloro derivative, m.p. 240°, and a bromo derivative, m.p. 247° (46). Saponification of the base with sodium hydroxide produces methyl alcohol and ricininic acid, C7H6O2N2, m.p. 320° (dec) (46, 51). Heating ricininic acid at 150° with fuming hydrochloric acid... 

A fourth and interesting route to ricinine (61) is based on the observation that the spontaneous polymerization of cyanoacetyl chloride gives rise to 2 4-dihydroxy-6-chloronicotinonitrile (6-chloronorricinine) (62). When the product of the reaction of the disodium salt of this compound with methyl sulfate is reduced with zinc and sulfuric acid, the so-called ricininic acid is produced. Conversion to the corresponding chloro compound and replacement of the halogen by a methoxyl completes the synthesis. 

These alkaloids include the substituted pyridone ricinine [524-40-3] (53), CgHgN202, which is easily isolated in high yield as the only alkaloid from the castor bean (Ricinus communis L.). The castor bean is also the source of castor oil (qv), which is obtained by pressing the castor bean and, rich in fatty acids, has served as a gentie cathartic. 

CjHgONa, which is obtained from ricinine by replacement of the methoxyl group by hydroxyl, chlorine and hydrogen in succession. Ricinidine, on hydrolysis, yields first an amide, C7Hg02N, and then a carboxylic acid, by ... 

The pyridine alkaloids anabasine (1), nicotine (2), ricinine (3), nomicotine (4) and trigonelline (5) form an important group of natural products. Thus anabasine (1) is extracted on a large scale in the Soviet Union (56MI20900) and functions as an insecticide with acute and subacute toxicity. Nicotine (2) has been used as an anthelmintic but more widely as an agricultural insecticide, functioning as a contact poison when combined with oleic acid... 

Ricinus communis L. Bi Ma Zi (Castor bean) (seed) Ricinine, ricinolein, olein acid, stearin acid, isoricinoleic acid, cytochrome C, castor oil.33-427-450 Cathartic, tumor inhibition. 

Ricinus communis L. China Ricinine, ricinolein, olein, stearin, isoricinoleic acid, cytochrome C.33 Cathartic. 

N.A. Ricinoleic acid, ricin, ricinine, lectins.99 The seeds are toxic. Laxative, prompting a bowel movement. 

Nicotinic acid undoubtedly provides the basic skeleton for some other alkaloids. Ricinine (Figure 6.35) is a 2-pyridone structure and contains a nitrile grouping, probably formed by dehydration of a nicotinamide derivative. This alkaloid is a toxic constituent of castor oil seeds (Ricinus communis Euphorbiaceae), though the toxicity of the seeds results mainly from the polypeptide ricin (see page 434). Arecoline (Figure 6.36) is found in Betel nuts (Areca catechu Palmae/Arecaceae) and is a tetrahydronicotinic acid derivative. Betel nuts are chewed in India and Asia for the stimulant effect of arecoline. 

Seeds of Areca catechu (betel nut) (Palmae) contain the simple jV-methyltetrahydropyridine 3-carboxylic acid (jV-methyl-A -tetrahydronicotinic acid) arecaidine and arecoline (arecai-dine methyl ester) (Section 1, Appendix) that are mACh-R agonists and accordingly parasympathetic stimulants. Betel nut also yields guvacine (A -tetrahydronicotinic acid) that is an anti-epileptic GABA transport inhibitor. Conversely the jV-methyl dihydropyridone derivative ricinine from seeds of Ricinus communis (castor seed) (Euphorbiaceae) is a stimulatory agonist acting at the benzodiazepine site of the GABA(A) receptor. 

The cyanogenic glucoside, acalyphin (Fig. 3.1), found in Acalypha indica, appears to be derived from nicotinic acid metabolism (Nahrstedt et al, 1982). Acalyphin is homologous to four non-cyanogenic 3-cyanopyridones, including ricinine, that have also been isolated from various Acalypheae (Nahrstedt, 1987). 

Ricinine.—Quinolinic acid (29) is known to be a precursor of ricinine (32). The results of other studies have indicated that the pyridine nucleotide cycle (Scheme 6)... 

Azaserine, a glutamine antagonist," is known to inhibit the NAD synthetase reaction in which nicotinic acid adenine dinucleotide is converted into NAD with glutamine or ammonia as the nitrogen donor. ° When azaserine or azaleucine was fed to Ricinus communis plants followed by [6- C]quinolinic acid, a marked decrease in incorporation of radioactivity into ricinine was observed with azaleucine, less so with azaserine." Both azaserine and azaleucine were found also to inhibit the incorporation of [6- " C]quinolinic acid into pyridine nucleotide cycle intermediates [in the case of azaserine the conversion of nicotinic acid dinucleotide into nicotinamide adenine dinucleotide (NAD ) was apparently inhibited]. 

Ricinine and ethionine were found to inhibit ricinine biosynthesis with shunting of radioactivity from [6- C]quinolinic acid through the pyridine nucleotide cycle into N-methylnicotinic acid (30) and N-methylnicotinamide (31) (c/. Scheme 6), and quinolinic acid consumption was reduced. 

These results strongly indicate a dependency between ricinine biosynthesis and the pyridine nucleotide cycle. The similarity in incorporation of members of this cycle into ricinine" is explained by allowing each member to be diverted directly into a pathway leading to ricinine this explanation covers the observation that excess exogenous NAD increases the incorporation of quinolinic acid into ricinine" since this precursor can simply be shunted along one of these diversions if the formation of NAD is blocked by its presence in large excess. 

A second route to ricinine was suggested by the observation that ethyl 2 4-dihydroxy-6-methyl-nicotinate is obtained from the condensation of ethyl malonate and ethyl /3-aminocrotonate in the presence of sodium ethylate (59). This substituted ethyl nicotinate when converted to the amide by means of alcoholic ammonia and dehydrated with phosphorus oxychloride gives rise to 2 4-dichloro-3-cyano-6-methylpyridine (LXXXYIII). Condensation of LXXXVIII with benzaldehyde followed by oxidation yields the acid (LXXXIX) and this on treatment with sodium methylate... 

Croton-oil—Oleum tiglii (TJ. S.)—Oleum crotonis (Br.)—varies much in color and activity, according to its source that which is obtained from the East is yellowish, liquid, transparent, and much less active than that prepared in Europe from the imported seeds, which is darker, less fluid, caustic in taste, and wholly soluble in absolute alcohol. Croton-oil contains, besides the glj -cerids of oleic, crotonieand fatty acids, about four per cent, of a peculiar principle called crotonol, to which the oil owes its vesicating properties. It also contains an alkaloid-like substance, also existing in castor-oil, called ricinin. Kone of these bodies, however, are possessed of the drastic powers of the oil Itself. 

Nicotinic acid is also a biogenetic precursor of ricinine (XCV) 143). By the use of tritiated nicotinic acid-7-i C and tritiated nicotinamide in... 

Leaves of Trewia mtdiflora L., a member of the Euphorbiaceae, were found t<5 contain a cyanopyridone alkaloid nudiflorine (CXXIX), C7H6N2O (mp 161°), reminiscent of the pyridone alkaloid ricinine (XCV) (187, 188). Hydrolysis of nudiflorine gives nudifloric acid (CXXX). Treatment of coumalic acid methyl ester (CXXXI) with ammonia... 

Ricinine.—Ricinine (49), the alkaloid of castor bean plants, is derived from nicotinic acid (28) and quinolinic acid (48), and its formation is intimately associated with the pyridine nucleotide cycle cf. ref. 6. Quinolinic acid is built from a C3 fragment that is formed from glycerol via glyceraldehyde and a C4 unit that is related to succinic or aspartic acids. A recent investigation has confirmed this pathway for ricinine (49) and indicated that dihydroxyacetone phosphate lies between glycerol and glyceraldehyde (loss of tritium from C-2 of labelled glycerol). ... 

Castor oH (ricinus oil). The oil obtained from seeds of the castor-oil plant or castor beans (Ricinus communis, Euphorbiaceae), mp. -10 C. It contains about 80-85% ricinoleic acid as glycerol ester together with oleic (7%), linolic (3%), palmitic (2%), and stearic (1%) acids. The Ricinus seeds contain the highly poisonous constituents ricin, a mixture of proteins, and ricinine, a pyridone alkaloid. The presence of these substances leaves the oilcake remaining after pressing of C. unsuitable for use as animal fodder. 

---