MXPA99007839A - Preparation of esterolic and stanoli esters - Google Patents

Abstract

The present invention relates to a method for the direct esterification of esanols and sterols with a catalyst, which can be stained or basic, in the presence of a color-deactivating agent for stanol / sterolic esters, the method provides a synthetic route that is applicable to large-scale production of high-yield esters, a preferred embodiment employs a food grade process free of organic solvents or mineral acids

Description

PREPARATION OF ESTEROLIC AND STANOLIC ESTERS FIELD OF THE INVENTION This invention relates to the preparation of discrete stanolic and esteric esters, through a highly efficient catalyzed route in the presence of a color deactivating agent.

BACKGROUND OF THE INVENTION It has been shown that the addition of plant sterols, such as β-sitosterol, to diets will reduce serum cholesterol levels. Sterols reduce cholesterol in the serum by interrupting the intestinal absorption of dietary cholesterol by displacing it from bile acid micelles. More recently, the saturated derivative of β-sitosterol, β-sitostanol, has been shown to be more effective in reducing the intestinal absorption of cholesterol. Sitoestanol itself is virtually unabsorbed, so it does not contribute at all to the concentration of serum sterol in vitro after consumption. Unfortunately, typical sterols and steels are insoluble in the micelle phase of the alimentary canal and have only limited solubility in oils and / or fats or water. Accordingly, the free sterols and stanols themselves are not optimal candidates for use in typical pharmaceutical or dietary dosage forms as cholesterol lowering agents. The patent of E.U. No. 5,502,045 describes the interesterification of tin cans with a fatty acid ester from an edible oil to produce a waxy ester-ester mixture with improved fat solubility characteristics. Specifically, this patent describes the reaction of interesterified sitoestanol with fatty acids of methyl esters of an edible oil, such as rapeseed oil, specifically by a base catalyzed transesterification reaction. This is a procedure that is widely used in the food industry. However, from a pharmaceutical point of view, interesterification processes like these have some different disadvantages. Firstly, the composition profile of the sterol-ester products is difficult to control since the profile depends on the fatty acid disposition present in the edible oil used in the reaction. In addition, methanol, a byproduct of this reaction, has to be removed very carefully and the use of methyl esters requires the use of large excesses, making recirculation difficult. In a different approach, German patent 2035069 describes the esterification of sterol esters to fatty acids by means of a process that is not food grade. In particular, thionyl chloride is used as a reagent which, when reacted, forms HCl gases as a by-product. Said techniques are not suitable for the production of food grade materials, and are generally undesirable. Japanese patent 76-11113 describes a catalyst-free esterification of higher fatty acid esters of related sterols or vitamins. However, this procedure employs a significant molar excess of fatty acid, a minimum of 25% up to 50%, which in turn requires the use of an alkali refining process to recover the ester product. The stoichiometric excess of fatty acid and the isolation techniques result in products that are discolored. From a pharmaceutical point of view, there is an unmet need for a method for the synthesis of discrete stanolic / esteric esters by means of a global food grade process. Discrete compounds are more desirable than blends for three main reasons: 1) the composition and performance specifications can be better controlled; 2) structure / activity studies are more feasible and 3) physicochemical and chemical properties can be controlled. These advantages of the stanolic / esterolic esters will be detailed later. In addition, there is a need for food grade esters of sterols / stanols that are of a clear color for the preparation of attractive food products. Procedures that reduce processing losses and equipment costs are also needed.

BRIEF DESCRIPTION OF THE INVENTION The present invention comprises a method for direct esterification of tin steels and sterols with catalysts, in the presence of a color activating agent to form discrete stanolic / sterolic esters. The catalyst can be a weak acid in the classical sense, or a Lewis acid, or traditional basic materials. The method provides a synthetic route that is applicable to the large scale production of the high yield and purity stanols by means of a food grade process which in a preferred embodiment is free of organic solvents or mineral acids and produces limited byproducts. The method finally provides a convenient method that makes it possible to design discrete stanolic / esteric esters with various physical and biological properties.

DETAILED DESCRIPTION OF THE INVENTION The present invention provides the direct esterification of tin and sterols by the reaction of stanol / sterol and fatty acids using acidic or basic catalysts. Β-sitostanol, the most preferred starting material, is produced commercially from β-sitosterol by a hydrogenation reaction and is commercially available from several sources, including Raisio Corporation.

The acids, which include the associated salts, reacted in the present invention contain from about 4 to about 24 carbon atoms. The acids include saturated acids, but are preferably unsaturated acids, including polyunsaturated acids. The saturated fatty acids reacted in the present invention have the formulas CH3- (CH2) n -CO2H, wherein n is an integer from 2 to 22, preferably n is from about 12 to about 20. The term fatty acid is well known and understood by those skilled in the art, see for example, Hawlev's Condensed Chemical Dictionarv, eleventh edition. The term includes the acids and salts of these acids. The fatty acids include saturated acids, such as stearic, butyric, lauric, palmitic and the like. Unsaturated fatty acids, including polyunsaturated fatty acids, can also be used in the present invention. Suitable unsaturated fatty acids include oleic, linoleic, linolenic, docosohexanoic, conjugated linoleic acid and the like. As described in the US patent. No. 5,554,646, column 1, lines 44-48, the conjugated linoleic acid is 9,11-octadecanoic acid, 10,12-octadecanoic acid and mixtures thereof. The present invention includes both straight and branched acids, with straight chain acids being preferred. In the present invention, the sterol and stanolic esters have the following general formula illustrated as Formula I: Formula I wherein Ri is understood to include straight or branched aliphatic carbon chains having a length of about C3-C24, preferably C6-C22 and most preferably C-? 2-C2? Groups, and it is understood that R2 includes straight or branched aliphatic carbon chains varying from C-5-C15, preferably from C6-C2 and most preferably Cg groups. More preferably, R2 is selected from the group of (dC-? 2) alkyl, (C? -C8) alkoxy, (C2-C8) alkenylene, (C2-C8) alkynyl, (C3-) cycloalkyl C8), halogenalkenyl of (C2-C8) and halogenoalkynyl of (C2-C8), wherein halogen includes chloro, fluoro, bromo, iodo and the like. Alkyl includes groups of carbon atoms of both straight and branched chain. Typical alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentyl, neopentyl, isopentyl, hexyl, heptyl and the like. The alkyl groups may be halogenated with one, two, three or more halogen atoms. The terms "alkenyl" and "alkynyl" include straight and branched chain hydrocarbons having at least one unsaturated bond.

The restoration in Cs provides the corresponding esterol ester.

Any stanol or sterol that is functionalized with a hydroxyl group is suitable for esterification by the process described herein. A generic formula of the stanols / sterols that can be esterified in the present invention is provided below: Formula II It is understood that R2 has the same meaning as mentioned above. Tinnels that are capable of being esterified in the present invention include, but are not limited to, β-sitoestanoi (illustrated in Figure Ill below), as well as other related compounds including cholestanol, ergoestanol, brassicaestanol, oatstanol, alpha-amyrin , cyclartenol, lupenol and the like.

For example, this method is also applicable to stellates such as DOsitoesterol (unsaturated in Cs, as shown in Figure Ill above). The molar ratios of the feedstocks for the esterification reaction, notably the stanol / sterol and the fatty acid, are provided at stoichiometric levels. In a highly preferred embodiment, the fatty acid is present in an excess of 5-10% to react all of the stanol. Any excess unreacted fatty acid is easily removed in the treatment of the product. Any catalyst can be employed in the present invention.

The catalyst can be weak acids, a Lewis acid or a basic catalyst. Suitable acid catalysts are described in the U.S. patent. No. 5,892,068, incorporated herein by reference. Suitable acid catalysts include toluene sulfonic acid, methanesulfonic acid, sodium hydrogen phosphate, sodium bisulfate, although mineral materials are not preferred. The proper catalyst that can act as a Lewis acid includes: iron chloride, iron oxide, magnesium oxide, manganese oxide, manganese chloride, sodium hydroxides, nickel chloride, tin oxide, tin chloride, like zinc oxide and zinc chloride. Some basic materials act as a catalyst for this reaction as well, such as sodium hydroxide. The catalyst is typically sufficient, if provided at 1 mole percent compared to the reagent level. As used herein, Lewis acid catalysts are understood to be compounds that are potential electron pair receptors. The catalyst level can be increased or decreased to provide the desired reaction rate, however, if too much catalyst is provided the result can be a higher level of the desired secondary reaction and products. Other suitable Lewis acid catalysts include boron trifluoride, aluminum chloride and the like. Any suitable Lewis acid can function as the catalyst, with zinc oxide being preferred as the catalyst. The catalyst can have a solid, liquid or gas form. One of the most effective aspects of the present invention is that the reaction is carried out in concentrated form, in which no solvents are added to the reaction mixture, thanks to the acid, in a preferred embodiment a fatty acid in a molten state, it acts as both a reactant and a solvent. It is particularly suitable to carry out the concentrated reactions in vacuo to remove the water from the reaction mixture, thereby bringing the reaction to conclusion and increasing the yield of the desired ester. Since water is not soluble in the product phase, much lower levels of fatty acids are required to bring the reaction to conclusion. The reaction temperature is located at temperatures of about 75 to about 225 ° C. The preferred scale is from about 100 to about 220 ° C and most preferably around 140 to 180 ° C. The reaction period can vary widely, but for better results and economy the reactions should be left until the conclusion. Reaction times of more than 12 hours are common, but not necessarily required. An advantage of the present invention is the high yield of the ester product provided by the process. The present process provides yields of more than 90% and preferably more than 95%. The reaction of the present invention is mild enough to prepare esters that have not been capable of being synthesized using methods previously described in the art. In particular, the present invention provides a method for preparing esters which are the reaction product of DHA (cis-4,7,10,13,16,19-docosahexaenoic acid) and CLA (octadecadienoic acid) and the sterol / stanol described above. These products are of particular interest since both DHA and CLA have been reported as possessing cholesterol-lowering properties. Therefore, a compound containing the combination of both stanol and sterol with a pendant ester functionality would be very beneficial, which when hydrolyzed would provide another cholesterol-limiting agent. The combination of these functions would be beneficial, since it is reported that DHA and CLA dissociate cholesteroi in the body through mechanisms different from those of the sterol and stanol products. The ester products of CLA and the sterol / stanol are provided below: Sterol / stanol octadecadienate; The 11-octadecadienoic form is illustrated above and the isomer 10, 12 is also common. Most preferably, ß-sitosterol octadecadienoate in a similar manner, the product of DHA ester and sterol / stanol is provided below: Docosahexaenoate of sterol / stanol, and very preferably docosahexaenoate of β-sitosterol and docosahexaenoate of β-sitostanol. The present invention also provides a method for reducing cholesterol in serum, in which an effective amount of CLA and DHA esters is used to reduce serum cholesterol. Typically, the level is from about 1 to about 20 g / day, preferably from about 3 to about 15, and most preferably from about 6 to about 9 a day.

Three isolation techniques such as those described below can be used to isolate the ester reaction product. Method A: Aqueous / organic solvent extraction isolation can be used to recover the stannic ester. Typical organic solvents include dichloromethane, chloroform or toluene. A typical aqueous / organic treatment was employed in which the ester was extracted in an organic solvent and subsequently isolated after evaporation. For example, the reaction mixture is cooled to room temperature, followed by the addition of CH2Cl2. The solution was then washed several times with aqueous NaHCO3. The fatty acid salts are separated in the aqueous phase and can be easily removed. The remaining organic phase containing the isolated ester is then dried over anhydrous NaSO * and decolorized with activated carbon. When non-chlorinated and light organic solvents (ie, hexane) are used for extraction, the formation of an inseparable emulsion is observed. Pure esters were recovered as solids or white oils after the removal of the solvent in a giatory evaporator and subsequent cooling. Method B: In an isolation technique that is preferred and used when the reaction is catalyzed with a weak acid, an amount of sodium hydroxide at least equal but not more than 10% molar excess of the acid used is added. to the esters dissolved in 10-15% water, based on the reaction mixture. After a gentle mixing, the water and soaps are allowed to drain. The material is then bleached and deodorized by common procedures for the edible oil industry. Since most of the excess fatty acids will remain in the ester product after washing, they will be recovered and recirculated from the deodorizer. Method C: In a most preferred isolation technique used for basic catalysts and some Lewis acid catalysts, the ester reaction product is isolated using only water. The crude reaction mixture is washed with 10% water which was allowed to separate for 1 to 2 hours and then drained. The resulting ester is then bleached with clay bleaching aids or edible oil bleaching silica to remove the color and soap residues present, and deodorized to remove excess fatty acids that are ready to be recirculated without further processing. Although all three methods produced esters of identical purity, the recovered yields (> 96%) were better with the C method. This method is also more applicable to large scale synthesis, because it gives a high purity product without the use of hazardous solvents that are not food grade. This method also has less interactions with the raw materials, which results in improved performance and reduced product losses. Method B is preferred over A, since it also provides improved yields when compared to A. Both B and C methods allow fatty acids to be recirculated more easily, reducing product costs.

The present invention provides several advantages over the described methods. The present invention provides a method for synthesizing substantially discrete stanolic esters in place of mixtures of stanolic esters. As used in the present, substantially discrete tries to say that the reaction product, the desired ester is provided in a very high proportion of the reaction product. Typically, the desired ester is provided in the reaction product by at least 90 weight percent, most preferably in an amount of at least about 98 percent, and if the reaction is allowed to reach at least 99 percent by cent in weight. The present invention is capable of essentially providing a single stanolic (esterolic) ester, with less than 0.2 weight percent of other ester products. The interesterification procedures described previously provide a mixture of the stannic ester products. For example, the methods described above provide mixtures of stanolic esters, commonly with broad scales of the present stanolic esters (for example, a mixture of 4 esters in ratios of 30, 30, 20, 20 percent by weight). Also in comparison, the direct esterification processes described previously use risky and harmful reagents. This production of discrete stanolic / esteric esters has several important advantages over the esterolic / esterolic ester mixtures produced by other processes. First, narrower performance specifications (ie, melting point, specific gravity, and structural purity of the species) are possible for discrete compounds. This is because the properties of the discrete compounds can be controlled more precisely than for the mixtures. Accordingly, suitable performance characteristics and the quality of the discrete esters are obtained more easily compared to a mixture of ester products. Moreover, since the present invention provides for the synthesis of discrete stanolic / esteric esters, structure / activity relationships can be discerned on a scale of fatty acid chain lengths. The determination of the structure / activity relationships, which are fundamental for a rational development of the drug, are only possible when analyzing discrete compounds. The total physical and physiological properties of the esterolic / stanolic ester can be controlled because those properties depend on which fatty acid is used. For example, esterification to unsaturated fatty acids (ie, oleic acid) can lead to low melting solids or even liquid products, whereas saturated fatty acid analogues (ie, stearic acid) tend to lead to flow solids. free of higher fusion. This ability to manipulate the physical properties of a high fusion sterol so extensively is quite unexpected. The present invention allows the selection of the ester to suit the desired physical properties. Free flowing solid material is desirable for the manufacture of compressed tablets, or for the incorporation of the stannic ester in confectionery products. These oil-type sterol / ester esters are advantageously used in the manufacture of soft gel dosage forms or incorporated into a salad dressing or yoghurt. A further advantage of the present invention is the ability to add a suitable amount of a color-deactivating agent during the reaction. Typically, the amount of the color deactivating agent is from about 0.05% to about 1% by weight, based on the total reaction weight; preferably about 0.15 to about 0.5% and most preferably about 0.25 to about 0.35 percent by weight. Suitable color deactivating agents include carbon, carbon and carbon black; edible oil, bleaching earth or a silica bleach such as Trisil from Grace Chemical, of which carbon or activated carbon is preferred. The color deactivating agent prevents the reaction product from becoming discolored, ie, not being white, and the color deactivating agent is preferably incorporated with each of the sterol / stanol and acid in the reaction vessel. The product resulting from the present invention is white, free of flavors and other volatile material with a soft flavor. The ester ester / ester ester product has a Gardner color value of less than 8, typically less than about 6, preferably less than about 4, and more preferably less than about 3 in the Gardner color scale. The Gardner color scale is known to those skilled in the art. The product of the reaction is configured in a block and the color block is compared with samples of a predetermined color. Previous procedures provided products with higher color values. For example, the stanolic esters produced according to the US patent. No. 5,892,068 had a color value of Gardner from about 9 to about 12. Using the procedure described in Japanese Patent 76-11113, the products would have Gardner color values of from about 10 to about 12. The reaction product can be dissolved in oil and added to any product food containing an oil component. Another advantage of the present invention is the elimination of the need for excessive soaps during the washing of the product to deactivate or remove any catalyst that may be contained in the resulting product. This improves the loss of yield reduction and accelerates the time for reactor completion. An additional advantage of the reaction is the ease of recirculating the excess fatty acids without further processing. Another advantage of the present invention is the production of a lower color product. A further advantage of the present invention is the use of a low excess of fatty acids. In other descriptions large excesses of the fatty acid source are required to bring the reaction to conclusion (commonly molar ratios of two fatty acids to a stanol / sterol). This makes cleaning, or processing after the reaction, difficult and expensive. The use of large excesses reduces the amount of product made in a certain reactor, increasing the cost of capital and increasing the cost of labor per kilo of product. Still another advantage of the present invention are the faster reaction times provided by the catalyzed reactions compared to the non-catalyzed reactions when carried out at the same reaction temperature. In addition to shorter reaction times, the resulting product also has a better color. For example, uncatalyzed reactions carried out at 250 ° C have reaction times of more than 13 hours. However, the catalyzed reaction, carried out under similar conditions such as batch size and reactor geometry, can be conducted at a much lower temperature, 170 ° C, and have reaction times for completion of 13 hours. Generally, the reaction times of the present invention vary from about 8 to about 15 hours, preferably 10 to about 14 and more preferably about 12 to about 13 hours. The term "acid" used herein to describe the acid used as the reagent includes saturated fatty acids, including polyunsaturated and polyunsaturated acids as described herein. The following examples are provided to better illustrate the claimed invention, but not to limit the invention to the examples provided below.

EXAMPLES The stannous-fatty acid esters of the invention were prepared by the catalyzed esterification reaction method as follows: stanol (10 mmol), fatty acid (12 mmol) and sodium bisulfate (0.12 mmol) were stirred in concentrated form under vacuum for 16 hours at 150 ° C. The resulting ester products were isolated using the technique described above as method A (using both water and an organic solvent) or method B (an aqueous separation process). When the glass-like products were formed in method A, they were converted into free-flowing solids after cooling to less than 0 ° C. Analyzes by gas chromatography of the crude reaction product indicated that the reactions proceeded to more than 95% completion. The final treatment was carried out according to methods A or B as described above. The analytical data for five representative stanolic esters are described below. Analytical data for a cholestanol ester is also included, as an additional model.

EXAMPLE 1 Β-sitostanol stearate was produced by the reaction of β-sitostanol and stearic acid. NaHSO4 was used as the catalyst and stigma-ethanol stearate was isolated using method A described above. The analytical results for the isolated stigma-ethanol stearate were as follows: 1 H NMR (CDCl 3): (4.60 (quintet, 1 H), 2.19 (t, 8, 2 H), 1.88 (d, 12, 1 H); IR (cnr) ? 1, KBr): 1739 (s, C = O), 1454 (m), 1388 (m), 1182 (s, CO), 725 (m); Elemental analysis for C47H86? 2: calculated: C 82.55% H 12.59%, found: C 82.70% H 12.50%, melting point (DSC): 103-105 ° C.

EXAMPLE 2 Β-sitostanol stearate was produced by the reaction of β-sitostanol and stearic acid. NaHSO4 was the catalyst used and stigma-ethanol stearate was isolated using method B described above. The analytical results for isolated compound are presented below: 1H-NMR (CDCI3): (4.62 (quintet, 1 H), 2.18 (t, 8, 2H), 1.88 (d, 12, 1 HOUR); IR (cm-1, KBr): 1739 (s, C = O), 1467 (m), 1381 (m), 1176 (s, C-O), 718 (m); Elemental analysis for C47H86? 2: calculated: C 82.55% H 12.59%, found: C 82.31% H 12.63%; PF (DSC): 101-104 ° C; % H2O (Karl Fischer) 0. 73%.

EXAMPLE 3 Β-sitostanol palmitate was produced by the reaction of β-sitostanol and palmitic acid. NaHS 4 was used as a catalyst and the stigma-ethanol palmitate was isolated using the procedure described above as method A. The analytical results for the isolated stigma-ethanol palmitate are presented below: 1 H NMR (CDCl 3): (4.68 (quintet, 1 H), 2.24 (t, 8, 2H), 1.95 (d, 12, 1 H), IR (cm "1, KBr): 1739 (s, C = O), 1460 (m), 1394 (m), 1176 (s, CO), 725 (m); Elemental analysis for C45H82O2: calculated: C 82.57% H 12.54%, found: C 82.59% H 12.53%, melting point (DSC): 102-104 ° C.

EXAMPLE 4 Β-sitostanol oleate was produced by the reaction of β-sitostanol and oleic acid. NaHS04 was used as a catalyst and the stigma-ethanol oleate was isolated using the technique described as method B. The analytical results are presented below: 1 H NMR (CDCl 3): (5.27 (m, 2H), 4.62 (quintet, 1 H), 2.23 (t, 8, 2H), IR (cirf, concentrated): 1739 (s, C = O), 1461 (m), 1387 (m), 1176 (s, C-O), 1010 (m); Elemental analysis for C47H84? 2: calculated: C 82.80% H 12.33%, found: C 82.98% H 12.36%; melting point (DSC): 41-44 ° C.

EXAMPLE 5 Cholestanol oleate was produced by the reaction of cholestanol and oleic acid. NaHS 4 was used as a catalyst and the cholestanol oleate was isolated using the technique described as method A. The analytical results are presented below: 1H-NMR (CDCl 3): (5.30 (m, 2H), 4.65 (quintet, 1 H), 2.22 (t, 8, 2H), IR (cm "1, concentrate): 1725 (s, C = O), 1454 (m), 1367 (m), 1168 (m, CO), 1003 (m ), 711 (m); Elemental analysis for C45HsoO2: calculated: C 82.67% H 12.25%, found: C 82.64% H 12.34%, melting point (DSC): 20-25 ° C.

COMPARATIVE EXAMPLE The reaction of cane oil and stanol by an interesterification route provides a product mixture having the following approximate and non-reproducible weight distribution: Stanol oleate 67% Stanol linoleate 19% Stanol linolenate 9% Stanol 3% palmitate .

EXAMPLE 6 A reaction was carried out using an oleic acid with a 1.05 molar excess and tin steels with 0.2% sodium bicarbonate as a catalyst. The addition of 0.2% activated carbon was done before the reaction started. The material was heated to 165 ° C and the water started as observed in the condenser. The reaction was heated to 170 ° C when the fatty acid levels had stopped, water was added and separated from the mixture. The color of the product was then classified as approximately 8 on the Gardner scale.

EXAMPLE 7 Example 6 was repeated without the carbon and the color of the washed product was 11+.

EXAMPLE 8 Example 6 was repeated using 0.2% zinc oxide as the catalyst. The product had a color of 9 on the Gardner scale. Examples 9 and 10 demonstrate the ease of employing the color deactivating agent in the present invention. Additional color enhancements can easily be obtained by modifying the amount of the color deactivating agent employed, as well as other variable procedures.

EXAMPLE 9 The reaction used in Example 6 was repeated without a catalyst. No reaction took place until the temperature was over 200 ° C and more than 10 hours at 235 ° C or higher reaction temperatures were required to complete the reaction. This demonstrates the benefits of the catalysts described herein, thereby allowing the reaction to proceed at lower temperatures and at a faster rate.

Claims (20)

NOVELTY OF THE INVENTION CLAIMS

1. - A method to produce stanolic / esterolic esters comprising: providing a stanol / sterol of the formula: provide an acid; reacting said stanol / sterol and acid in the presence of a sufficient amount of catalyst and a sufficient amount of a color-deactivating agent to form the corresponding substantially discrete stanolic / sterolic ester of the formula: wherein R-i is a carbon chain having a length of about C5-C25 and R2 is a carbon chain having a length of about C3-C15.

2. - The method according to claim 1, further characterized in that the reaction is carried out concentrated, with the acid acting as the solvent.

3. The method according to claim 1, further characterized in that the catalyst is basic in water.

4. The method according to claim 3, further characterized in that the catalyst is zinc oxide.

5. The method according to claim 1, further characterized in that the corresponding ester / esterolic ester is provided in an amount of not less than about 98% by weight.

6. The method according to claim 1, further characterized in that R-i of the esterolic / esterolic ester has a value of approximately C-? 2 to C2 ?.

7. The method according to claim 1, further characterized in that the reaction temperature is from about 100 to about 220 ° C.

8. The method according to claim 1, further characterized in that the reaction is carried out under vacuum.

9. The method according to claim 1, further characterized in that the isolation of the corresponding ester / esterol ester is carried out in a completely aqueous process.

10. - The method according to claim 1, further characterized in that the color deactivating agent is carbon or activated carbon.

11. The process according to claim 1, further characterized in that the amount of color deactivating agent is from about 0.05 to about 1 weight percent, based on the total weight of the reaction.

12. A method for producing stanolic / esterolic esters comprising: providing a stanol / sterol of the formula: provide a polyunsaturated fatty acid having a length of Cß to C24 carbon atoms; reacting said stanol / sterol and fatty acid in the presence of a sufficient amount of catalyst and an effective amount of a color-deactivating agent, resulting in the production of the corresponding substantially discrete stanolic / sterolic ester.

13. - The method according to claim 12, further characterized in that the reaction is carried out concentrated, the polyunsaturated fatty acid acting as the solvent.

14. The method according to claim 12, further characterized in that the catalyst is a Lewis acid.

15. The method according to claim 14, further characterized in that the Lewis acid is zinc oxide.

16. The method according to claim 12, further characterized in that the corresponding ester / esterol ester is provided in an amount of not less than about 98% by weight.

17. The method according to claim 12, further characterized in that the reaction temperature is from about 100 to about 220 ° C.

18. The method according to claim 12, further characterized in that the reaction is carried out under vacuum.

19. The method according to claim 12, further characterized in that the isolation of the corresponding ester / esterol ester is carried out in a completely aqueous process.

20. A method for producing stanolic / esterolic esters comprising: providing a stanol / sterol of the formula: providing an acid, reacting said stanol / sterol and acid in the presence of a sufficient amount of Lewis acid catalyst; and optionally a sufficient amount of a color-deactivating agent, to form the corresponding substantially discrete stanolic / sterolic ester of the formula: wherein R-- is a carbon chain having a length of about C3-C24 and 2 is a carbon chain having a length of about C3-C15.