Nicotinic acid esters from

Nicotinyl alcohol (3-pyridinylcarbinol, 3-pyridinemethanol) (27) has use as an antilipemic and peripheral vasodilator. It is available from either the reductions of nicotinic acid esters or preferably, the reduction of the nitrile to the amine followed by dia2otation and nucleophilic displacement. It is frequently adininistered in the form of the tartrate (Eig. 7). Nicotinic acid is frequently used as a salt in conjunction with basic dmgs such as the peripheral vasodilator xanthinol niacinate (28). Nicotinic acid and its derivatives have widespread use as antihyperlipidemic agents and peripheral vasodilators (1). 

Table 1 The values (min) of nicotinic acid esters omitted from Eqs. 30 and 31, and predicted by these equations...

Testosterone Nicotinate. I7-[(3-Pyridinylcarbon-yt)oxyJandrost-4-en-3-one testosterone 17-nicotinic acid ester Bolfortan. CjjHjtNOj mol wt 393.51. C 76.30%, H 7.94%, N 3.56%, O 12.20%, Prepared from testosterone and nicotinic acid anhydride Zirm, Weichsel, U.S. pat. 3,057,-856 (1962 to Lannacher Heilmittel). 

Source From use of traditional stmctural descriptors in QSRR analysis of nicotinic acid esters, in J. Liq. Qiromatogr. Relat. Technol. 

Fig. 1 Relationship between the experimental /r (min) values of nicotinic acid esters and the r values calculated using Eq. 29. Source From Use of traditional structural descriptors in QSRR analysis of nicotinic acid esters, in J. Liq. Chromatogr. Relat. Technol.f ...

Figure 11.20 Stabilization quotient Q of nicotinic acid esters (ethyl, isopropyl, butyl, benzyl and hexyl) as a function of percentage binding of ester, (a) to three non-ionic surfactants based on PEG lOCX) O PEG l(X)0-lauryl ether, X PEG l(XX)-myristyl ether, PEG 1000 palmityl ether, and (b) to three stearyl surfactant derivatives, O PEG 900 stearyl ether, X PEG 1400 stearyl ether and PEG 2000 stearyl ether. In both (a) and (b) ionic strength is 0.083, temperature 20.0 0.1° C and borate buffer pH 10.(X) 0.02 used. Redrawn from Lippold et al [137], by permission.

From a bioavailabihty standpoint, the fact that a significant amount of nicotinic acid is in a bound form has important biological consequences. Poor bioavailabihty stems from the fact that the ester linkage is resistance to digestive enzymes. In the case of com, this condition can be alleviated if com is pretreated with alkah. This food preparation method is frequently practiced in Mexico for the preparation of tortillas. 

In the rosary pea Abrus precatorius L. Trigollenine as well as its gallic acid ester Precatorine (209) is found (71P195) (Scheme 69). 1-Carboxymethyl-nicotinic acid (210) was isolated as a colorless solid from the marine sponge Anthosigmella cf. raromicrosclera as a cysteine protease inhibitor (98JNP671). This compound was first synthesized in 1991. The sodium... 

In view of the biological importance of nicotinic acid, it was decided to prepare a quaternary salt from the acid or ester and bromofluoroethane. S Carbethoxy- N-2-fluoroethylpyridinium bromide (XIX) was therefore prepared and examined. The l.d. 50 for subcutaneous injection into mice was 200 mg. /kg., i.e. it was relatively non-toxic compared with methyl fluoroacetate. 

Nicotine Nicotine, l-methyl-2-(3-piridyl)pirrolidine (13.1.27), is an alkaloid that is isolated from the plant Nicotiana (Nicotiana tabacum, Nicotiam rustica, and others) and can be synthesized in varions ways [33-36]. In particular, it is proposed to proceed from nicotinic acid ethyl ester, which is condensed with iV-methylpyrrolidone, giving l-methyl-2-nicotinoyl pyrrolidone-2 (13.1.23). Acidic hydrolysis of this compound leads to an opening of the pyrrolidine ring giving the intermediate (13.1.24), which under the reaction conditions is decarboxylated to the /-aminoketone (13.1.25). The carbonyl group is reduced to an alcohol and the resnlting prodnct (13.1.26) undergoes dehydration to nicotine (13.1.27). 

Hydroxycynnclidine (14.1.17) is synthesized from the methyl ester of wo-nicotinic acid, which is reacted with the ethyl ester of bromoacetic acid to give the piridinium salt (14.1.14). This is rednced by hydrogen nsing a platinnm catalyst, giving 1-carbethoxymethyl-... 

Hydrolases, which catalyze the hydrolysis of various bonds. The best-known subcategory of hydrolases are the lipases, which hydrolyze ester bonds. In the example of human pancreatic lipase, which is the main enzyme responsible for breaking down fats in the human digestive system, a lipase acts to convert triglyceride substrates found in oils from food to monoglycerides and free fatty acids. In the chemical industry, lipases are also used, for instance, to catalyze the —C N —CONH2 reaction, for the synthesis of acrylamide from acrylonitril, or nicotinic acid from 3-pyridylnitrile. 

Furo[3,4-r]pyridine derivatives are generated from the reaction of 2,3-dihalopropenyl ketones with the ethyl ester of / -aminocrotonic acid. Initial reaction products are substituted nicotinic acids which can be partially converted into the furopyridines under harsh vacuum distillation conditions (Scheme 12) <2005CHE1009>. 

An iron-catalyzed reaction of an a,P-unsaturated oxime such as 68 with a P-oxo ester also gave pyridine derivatives such as nicotinic acid 69 [99]. Under the reaction conditions (150-160 °C, without solvent) first Michael adducts such as intermediate 70 are presumably formed, which further condense via intermediate 71. This method is not restricted to a centric symmetry in the substitution pattern, which is an advantage compared with the Hantzsch synthesis. Moreover, the method starts with hydroxylamine being two oxidation stages above ammonia therefore, no oxidation in the final stage from dihydro- to pyridine is necessary (Scheme 8.31). 

The interesting formation of 3-methylenepiperidine (68) (along with 3-methylpyridine and 3-methylpiperidine) was observed in the electrolytic reduction of 3-formylpyridine and 3-pyridylcarbinol.58 Nipecotinic acid and guvacine (69) are obtained from nicotinic acid or its esters.59 (For a discussion of guvacine, see Section V,A.)... 

Nicotinic acid (hut not nicotinamide) causes a marked vasodilatation, with flushing, burning, and itching of the skin. Very large single doses of nicotinic acid may cause sufficient vasodilatation to lead to hypotension after the administration of 1 to 3 g of nicotinic acid daily for several days, the effect wears off to a considerable extent. A number of nicotinoyl esters have been developed to permit sensitive patients to benefit from the hypoUpidemic effect of... 

The greatest hazard to life arises from suppression of the ability to secrete sweat, which can give rise to fatal hyperthermia if body temperature is not controlled artificially during hot weather or strenuous activity. Another source of hazard to life arises from the effect of the compounds other than scopolamine and its quaternary form in accelerating heart rate and facilitating Intramural conduction and transmission of Impulses. Ihese actions may result in serious arrhythmias up to and including ventricular fibrillation. The quaternary amine forms of the tropic acid esters in which we are interested are more active in some respects than the tertiary amines, as far as peripheral actions are concerned. This is especially true with respect to actions on nicotinic effectors in ganglia and striated muscles. The quaternary amines penetrate into the central nervous system poorly, but, once there, affect muscarinic effectors in the same way as the tertiary amines. 

Glycosides of this vitamin (sometimes denoted as vitamin B3) were not described, however, there exists an evidence that bound niacin from wheat bran (termed niac)4in) has a single nicotinic acid moiety at least partially linked to an aromatic amine with glucose, xylose, and arabinose in a 6 3 1 molar ratio per molecule, with approximately three cinnamic acid esters [152,177,178]. It seems that these glycosidic complexes limit the bioavailability of the nicotinamide and for its liberation they must be treated, e. g., by soaking com in a lime solution, traditionally performed in Central America during production of tortillas [179]. 

Pyka and Sliwiok separated six esters of nicotinic acids methyl nicotinate, ethyl nicotinate, isopropyl nicotinate, butyl nicotinate, hexyl nicotinate, and benzyl nicotinate by adsorption HPLC on a LiChrospher Si 60 column. The mixtures containing benzene and methanol in volume proportions (O-i-lO, 1h-9, 2h-8, 3h-7, 4-1-6, and 5-1-5) were used as the mobile phases. The (min) values of esters investigated have been correlated with the dipole moments (/imph) of the mobile phases apphed, with numerical values of one topological index from among those based on the distance matrix (A, W, °7J, B) or the... 

Equations 28 and 29 can also be used to predict the Jr values of the esters of nicotinic acid, whose measurement points have not been taken into consideration in the equation. A test was performed on Eqs. 28 and 29 to determine how well they predict r values of points not included in the training set. Three values were removed from the training sets (Eqs. 28 and 29). Isopropyl nicotinate (separated in benzene methanol, 5 5, voFvol) and ethyl nicotinate (separated in benzene methanol, 4 6, and 0 10, voFvol) from Eqs. 28 and 29 were removed. This subset of two parametric equations was recalculated as ... 

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