Eastman-kodak Company

Eastman Chemical Company

Abbott Laboratories Corporation

Other

Rhone-poulenc Nutrition Animale

Charles A McCombs

Terrence B Mazer

Charles H Foster

Robert J Clemens

Ronald H Birkhahn

Robert Alan Miller

Charles Edwan Sumner, Jr

Scott Donald Barnicki

John Anthony Hyatt

Stephen H Wu

Charles T Goodhue

John C Hubbs

Stephen Weinhold

Pierre Autant

Ernest Phillip Smith

James C Phillips

Jacques Ruel

Louis P Hoskins

Gwendolyn C Kydd

Tommy L Tackett

This invention is directed to the use of triglycerides containing fatty ester moieties that include arachidonic acid (AA) and docosahexaenoic acid (DHA) in enteral nutritionals or nutritional supplements. These triglycerides are derived from lipid mixtures which have high levels of sterols and phosphorous. A preferred embodiment of the invention comprises an infant or enteral nutritional, or nutritional supplement, that comprises a lipid source derived from egg yolk. The lipid source derived from egg yolk is prepared by transesterification or hydrolysis, subjecting the mixture to distillation, and esterification with glycerin to result in a triglyceride containing the desired fatty acids of AA and DHA and little or no sterols and phosphorus.

Enteral formula or nutritional supplement containing arachidonic and docosahexaenoic acids

Disclosed is a process for the synthesis of 3-buten-1-ol by contacting 3,4-epoxy-1-butene and formic acid with a homogeneous catalyst solution comprising a palladium(0) compound, a tertiary phosphine and a trialkylamine dissolved in tetrahydrofuran.

Preparation of 3-buten-1-ol from 3,4-epoxy-1-butene

Fatty acid esters such as those containing arachidonic acid (AA) and docosahexaenoic acid (DHA) derived from lipid mixtures are prepared with reduced levels of sterols and phosphorus. A preferred embodiment of the invention comprises extracting lipids from egg with methanol; separating lipids including sterols from insoluble egg components; submitting the methanolic solution of lipids to transesterification and subsequent neutralization to convert the lipids to methyl esters of said free fatty acids together with sterols; separating the said sterols and esters from an aqueous phase including phosphorus compounds formed in the transesterification; subjecting the said fatty acid esters and sterols to distillation to separate sterols from the fatty acid esters; and subjecting the said esters to transesterification in the presence of glycerol to produce triglycerides of said esters thereof including that of AA and DHA wherein the resulting triglycerides contain reduced quantities of sterols and phosphorus.

Polyunsaturated fatty acids and fatty acid esters free of sterols and

A process for the production of water soluble glycerol esters useful as parenteral nutrients is disclosed. The process comprises the reaction of glycerol or a protected glycerol and an acetoacetate ester or acetoacetate precursor, yielding an acetoacetyl glycerol which is thereafter reduced, providing a glycerol ester of 3-hydroxybutyric acid.

Nutritive water soluble glycerol esters of hydroxy butyric acid

Novel compositions that are useful as nutrients are disclosed. These compounds are preferably water soluble parenteral nutrients and are glycerol esters of .beta.-acyloxybutyrates of the formula ##STR1## wherein each R is the same or different and is hydrogen, or --COCH.sub.2 CHOR'CH.sub.3), provided that at least one R is not hydrogen and wherein R' is a linear acid ester of even carbon number from 2 to 20 carbons. These compositions are useful as a substitute for glucose in feeding.

Nutritive glycerol esters of .beta.-acyloxy butyrates

Preparing cyclohexanediones of the formula ##STR1## an aldehyde is reacted with a ketene to give a polymer having the repeating unit ##STR2## wherein n ranges from about 2 to about 1,000. The polymer is hydrolyzed to produce a mixture of an unsaturated acid of the formula R--CH.dbd.C(R.sub.1)--COOH and a hydroxy ester or acid of the formula R--CH(OH)C(R.sub.1)(R.sub.2)--COOR.sub.3, the mixture is then contacted with an esterifying agent to convert the acids to esters. The ester mixture is contacted with a dehydrating agent to convert the hydroxy ester to unsaturated ester of the formula R--CH.dbd.C(R.sub.1)--COOR.sub.3. The unsaturated ester is contacted with a basic catalyst to cyclize it to the cyclic dione ester of the formula ##STR3## and this ester is then hydrolyzed and decarboxylated to give the cyclohexanedione give the product wherein:

Organic compositions and their manufacture

Preparation of cyclohexanediones of the formula ##STR1## are disclosed. An aldehyde of the formula R--CHO is reacted with a ketene type compound of the formula (R.sub.1) (R.sub.2) C.dbd.C.dbd.O to give a polymer: ##STR2## wherein n ranges from about 2 to about 1,000. The polymer is hydrolyzed to produce a mixture of an unsaturated acid of the formula R--CH.dbd.C(R.sub.1)--COOH and a hydroxy ester or acid of the formula R--CH(OH)C(R.sub.1) (R.sub.2)--COOR.sub.3, the acids in the mixture are converted for esters. The hydroxy ester of the ester mixture is converted to unsaturated ester of the formula R--CH.dbd.C(R.sub.1)--COOR.sub.3. The unsaturated ester is contacted with a basic catalyst to cyclize it to the cyclic dione ester of the formula ##STR3## and this ester is then hydrolyzed and decarboxylated to give the product ##STR4## wherein: R is selected, e.g., from alkylthio, alkylthioalkyl, cycloalkyl, alkyl substituted cycloalkyl, alkoxy, alkanoyloxy, alkoxycarbonyl, aryl, substituted aryl, heterocylcic, or substituted heterocyclic, wherein each group or moiety has up to 20 carbons; and

The present invention relates to new granules, as well as the process for their preparation, obtained by extrusion of a mixture containing a meltable binder in an amount such that it permits the passage of the mixture through a die. The granules obtained are then coated with a polymer permitting their trans-rumen passage without degradation. After coating, these granules are used for animal feeding of ruminants.

Extrusion of an admixture of a meltable binder and a food or drug

Processes, intermediates, and products involved in preparing cyclohexanediones of the formula ##STR1## are disclosed. An aldehyde of the formula R--CHO is reacted with a ketene type compound of the formula (R.sub.1)(R.sub.2)C.dbd.C.dbd.O at a temperature below about 110.degree. C. to give a polymer having the repeating unit ##STR2## wherein n ranges from about 2 to about 1,000. The polymer is hydrolyzed with alcoholic or aqueous base to produce a mixture of an unsaturated acid of the formula R--CH.dbd.C(R.sub.1)--COOH and a hydroxy ester or acid of the formula R--CH(OH)C(R.sub.1)(R.sub.2)--COOR.sub.3, the mixture is then contacted with an esterifying agent to convert the acids to esters. The ester mixture is contacted with a dehydrating agent to convert the hydroxy ester to unsaturated ester of the formula R--CH.dbd.C(R.sub.1)--COOR.sub.3. The unsaturated ester is contacted with a basic catalyst to cyclize it to the cyclic dione ester of the formula ##STR3## this ester is then hydrolyzed and decarboxylated to give the product ##STR4## wherein: R is selected, e.g., from alkylthio, alkylthioalkyl, cycloalkyl, alkyl substituted cycloalkyl, alkoxy, alkanoyloxy, alkoxycarbonyl, aryl, substituted aryl, heterocyclic, or substituted heterocyclic, wherein each group or moiety has up to 20 carbons; and

A method for obtaining a stigmasterol enriched product from esterified deodorizer distillate by use of a particular solvent system. The solvent system contains water, a C.sub.1 to C.sub.6 alcohol such as methanol, and a non-polar solvent such as heptane.

Method for obtaining a stigmasterol enriched product from deodorizer

Processes, intermediates, and products involved in preparing cyclohexanediones of the formula ##STR1## are disclosed. An aldehyde of the formula R--CHO is reacted with a ketone type compound of the formula (R.sub.1)(R.sub.2)C.dbd.C.dbd.O at a temperature below about 110.degree. C. to give a polymer having the repeating unit --OCH(R)C(R.sub.1)(R.sub.2)CO].sub.n wherein n ranges from about 2 to about 1,000. The polymer is hydrolyzed with alcoholic or aqueous base to produce a mixture of an unsaturated acid of the formula R--CH.dbd.C(R.sub.1)--COOH and a hydroxy ester or acid of the formula R--CH(OH)C(R.sub.1)(R.sub.2)--COOR.sub.3, the mixture is then contacted with an esterifying agent to convert the acids to esters. The ester mixture is contacted with a dehydrating agent to convert the hydroxy ester to unsaturated ester of the formula R--CH.dbd.C(R.sub.1)--COOR.sub.3. The unsaturated ester is contacted with a basic catalyst to cyclize it to the cyclic dione ester of the formula ##STR2## and this ester is then hydrolyzed and decarboxylated to give the product ##STR3## wherein: R is selected, e.g., from alkylthio, alkythioalkyl, cycloalkyl, alkyl substituted cycloalkyl, alkoxy, alkanoyloxy, alkoxycarbonyl, aryl, substituted aryl, heterocyclic, or substituted heterocyclic, wherein each group or moiety has up to 20 carbons; and

Acetoacetic esters of the formula R--OOCCH.sub.2 COCH.sub.3 are reacted with an unsaturated ester of the formula R.sup.1 R.sup.2 C.dbd.CHCOOR.sup.3 in the presence of basic catalyst such as ethanolic sodium ethoxide to give compound I of the formula ##STR1## and the alcohol by-product HOR.sup.3. By known hydrolysis and decarboxylation procedures, compound I is convertible to compound II of the formula ##STR2## In the above formulas, R is alkyl, R.sup.1 and R.sup.2 are each selected independently from H, alkyl, alkylthioalkyl, cycloalkyl, alkyl substituted cycloalkyl, aryl, substituted aryl, heterocyclic, or substituted heterocyclic, and R.sup.3 is alkyl or cycloalkyl. These compounds I and II are intermediates in the preparation of known herbicides.

Preparation of 4-carboalkoxy-1,3-cyclohexanedione type compounds

Disclosed herein is a method for preparing 11.beta., 17.alpha., 20, 21-tetrahydroxy steroids of the pregnane class. This method comprises incubating the corresponding 17.alpha., 20.alpha. or .beta., 21-trihydroxy steroid in the presence of a culture medium capable of effecting the 11.beta.-hydroxylation, such medium comprising a fungal culture of the genus Curvularia. Also disclosed herein is a method for preparing 11.beta., 17.alpha., 21-trihydroxy-20-oxo steroids of the pregnane class. This method comprises the hydroxylation method described hereinabove followed by conversion of the resulting 11.beta., 17.alpha., 20.alpha. or .beta., 21-tetrahydroxy steroid into the corresponding 11.beta., 17.alpha., 21-trihydroxy-20-oxo steroid.

Method of preparing 11.beta., 17.alpha., 20, 21-tetrahydroxy steroids

In accordance with the present invention, 17.alpha.-hydroxy-20-ketosteroids are prepared by the oxidation of 20-ketosteriods, such as 3-methoxy-pregna-3,5-dien-20-one. The 3-methoxypregna-3,5-dien-20-one is prepared from progesterone by methods well known in the art. The pregn-20-ones, such as 3-methoxypregna-3,5-dien-20-one, are oxidized with oxygen or air using a base catalyst in the presence of a phosphite reducing agent in a suitable solvent. The base catalyst consists of an alkali metal tert-alkoxide, which can be prepared from an alkali metal and a tert-alkanol. The oxidation reaction can be carried out at any temperature from about -20.degree. C. to about 50.degree. C. and for a period of 2-20 hours depending on the temperature at which the reaction is carried out. For example, at ambient temperature the rate of oxidation is sufficiently fast to complete the oxidation in 2 to 4 hours. This method for preparing 17.alpha.-hydroxy-20-ketosteroids from 20-ketosteroids is an important and valuable step in preparing corticosteroids and other hormones.

Process for preparing 17.alpha.-hydroxy-20-ketosteroids

The present invention provides a non-fermentation process for placing unsaturation at the 9,11 position in a steroidal compound. Also, the present invention provides a process whereby the modified steroidal compound can be separated from the reaction mixture without the use of chromatography. More specifically, the present invention provides a process whereby a steroid compound such as 17-.alpha.-hydroxy-progesterone is reacted to form the meta iodoaryl benzoate. The iodoarylbenzoate is then irradiated with visible light in the presence of an alkyl-m-iodobenzoate dichloride to form the 9.alpha.-chloro steroid derivative. The chlorinated steroid derivative can then be hydrolized to provide a 9.alpha.-chloro steroidal alcohol and m-iodobenzoic acid. The m-iodobenzoic acid is extracted by the use of an aqueous base. The chlorinated steroidal alcohol can then be recovered and converted by conventional dehalogenation techniques to steroidal unsaturated compound having a double bond in the 9,11 position of the steroid nucleus. Alternatively, the chlorinated steroid derivative can be dehalogenation and then hydrolized.

Growing community of inventors

Kingsport, TN, United States of America

Charles A McCombs