161 results about "Cyclopropanation" patented technology

The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

Chiral ruthenium catalysts comprising salen and alkenyl ligands are provided for stereoselective cyclopropanation, and methods of cyclopropanation are provided. The chiral ruthenium catalyst is prepared in situ by combining an alkenyl ligand, a deprotonated chiral salen ligand, and a ruthenium (II) metal. A preferred catalyst is prepared in situ by combining 2,3-dihydro-4-venylbenzofuran, deprotonated 1,2-cyclohexanediamino-N,N′-bis(3,5-di-t-butyl-salicylidene) and RuCl2(p-cymene)]2.

A method of producing 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one comprising subjecting a cyclopropane compound of the formula (1):(wherein, R1 represents an alkyl group, R2 represents an alkyl group having carbon atom(s) of 1 to 10, a haloalkyl group having carbon atom(s) of 1 to 10, or an aryl group having carbon atoms of 6 to 10 optionally substituted by an alkyl group having carbon atom(s) of 1 to 10, and when R2 represents the alkyl group, R1 and R2 are optionally the same or different each other.) to any of the following reactions a), b) and c):a) an acid treatment reaction after an alkali hydrolysis reactionb) an acid hydrolysis reactionc) an enzyme hydrolysis reaction , then, removing an aqueous layer.

Chiral ruthenium catalysts comprising salen and alkenyl ligands are provided for stereoselective cyclopropanation, and methods of cyclopropanation are provided. The chiral ruthenium catalyst is prepared in situ by combining an alkenyl ligand, a deprotonated chiral salen ligand, and a ruthenium (II) metal. A preferred catalyst is prepared in situ by combining 2,3-dihydro-4-venylbenzofuran, deprotonated 1,2-cyclohexanediamino-N,N′-bis(3,5-di-t-butyl-salicylidene) and RuCl2(p-cymene)]2.

The invention relates to a preparation method of 1-(4-chlorphenyl)-2-cyclopropyl-1- rolactone(I) and cyclopropanation of 1-(4-chlorphenyl)-2-methyl-3-butylene-1-ketone(II); and the 1-(4-chlorphenyl)-2-methyl-3-butylene-1-ketone(II) is produced by the reaction of parachloronitrile, crotyl chloride, zinc powder in tetrahydrofuran and alchlor and alchlor can also not be applied; (II) is reacted with dibromomethane, zinc powder in organic solvent and cuprous chloride to produce 1-(4-chlorphenyl)-2-cyclopropyl-1- rolactone(I). Midbody (II) can not be separated and cleaned in the process of reaction.

Chiral ligands and transition metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The chiral ligands include phospholanes, P,N ligands, N,N ligands, biphenols, and chelating phosphines. The ferrocene-based irridium (R,R)-f-binaphane complex reduces imines to the corresponding amines with 95-99.6% enantioselectivity and reduces beta-substituted-alpha-arylenamides with 95% enantioselectivity. The transition metal complexes of the chiral ligands are useful in asymmetric reactions such as asymmetric hydrogenation of imines, asymmetric hydride transfer reactions, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, allylic alkylation, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition and epoxidation reactions.

Chiral ligands and transition metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The chiral ligands include (R,S,S,R)-DIOP*. The ruthenium complex reduces enamide to the corresponding amine with up to 99% enantioselectivity. The transition metal complexes of the chiral ligands are useful in asymmetric reactions such as asymmetric hydrogenation, hydride transfer, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydrocarboxylation, isomerization, allylic alkylation, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition and epoxidation reactions.

The invention relates to a method for preparing a hydrochloride of 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole. The method is to subject 2,4-difluorophenyl(4-piperidinyl) ketoxime or a hydrochloride thereof to cyclopropanation and salifying in an aprotic solvent containing an alkali metal hydroxdide, wherein the molar ratio of the 2,4-difluorophenyl(4-piperidinyl) ketoxime or a hydrochloride thereof to the alkali metal hydroxide is 1 to between 1 and 3. The method can effectively prevent F atoms on para positions from participating in the reaction and avoid the production of a dipolymer (V), thereby avoiding the production of a dipolymer (VI) during the following preparation of risperidone. The method crystallizes crystals of a target substance directly by salifying, thereby solving the problems of use of a plurality of kinds of organic solvents, complex operation and low yield due to the extraction by toluene, condensation, and crystallization of petroleum ether. The yield rate of the target substance is more than 80 percent, and the purity of target substance is more than 99 percent.

The present invention provides a compound having aggrecanase inhibitory activity and MMP-13 inhibitory activity, and useful as a therapeutic agent for osteoarthritis, rheumatoid arthritis and the like, more specifically, a cyclopropane compound of formula (1):wherein R1 is —(CH2)m—X—(CH2)n-A1 etc., wherein m and n are the same or different and each is 0 to 6, X is a single bond, etc. and A1 is a substituted C3-14 hydrocarbon ring group, etc.; R2 and R3 are the same or different and each is a hydrogen atom, —(CH2)p—X1—(CH2)q-A2, etc., wherein p and q are the same or different and each is 0 to 6, X1 is a single bond, etc. and A2 is an optionally substituted C3-14 hydrocarbon ring group, etc.; R4 is —CO2R9, etc., wherein R9 is a hydrogen atom, etc.; and R20 and R21 are the same or different and each is a hydrogen atom, —(CH2)m12—X12—(CH2)m12—R30, etc., wherein m12 and m12 are the same or different and each is 0 to 6, X12 is a single bond, etc. and R30 is a hydrogen atom, etc.; or a prodrug thereof or a pharmaceutically acceptable salt thereof.

The present invention provides a compound having aggrecanase inhibitory activity and MMP-13 inhibitory activity, and useful as a therapeutic agent for osteoarthritis, rheumatoid arthritis and the like, more specifically, a N-substituted-N-sulfonylaminocyclopropane compound of formula (1): wherein R1 is —W-A1—W1-A2, W is —(CH2)m—X—(CH2)n—, wherein W1 is —(CH2)m1—X1—(CH2)n1—, m, m1, n and n1 are the same or different and each is 0 to 6, X and X1 are the same or different and each is a single bond, etc., A1 is an optionally substituted C3-14 hydrocarbon ring group, etc. and A2 is a substituted C3-14 hydrocarbon ring group etc.; R2 is —(CH2)r—CO—R8, etc., wherein r is 0 to 6 and R8 is a C1-6 alkoxy group, etc.; R3 and R4 are the same or different and each is a hydrogen atom, a C1-6 alkyl group, etc.; and R5 is —CO2R21 etc.; R30 and R31 are the same or different and each is a hydrogen atom, etc.; or a prodrug thereof or a pharmaceutically acceptable salt thereof.

A carried catalyst used for cyclopropanizing 2,5-dimethyl-2,4-hexadiene contains the active component (20-90%) chosen from Fe, Ca, Ni, Ca, Zn, Cr, Mo or Ti, the assistant (0.1-5%) chosen from L, Na or K, and the carrier chosen from alumina silica gel and activated carbon. It is prepared through premodifying carrier, and immersing while adding active component and the organic compound containing hydroxy or carboxyl group and oxygen. Its advantages are low dosage, high output rate, little coking and easy separation.

A compound selected from those of formula (I): wherein:p represents an integer of from 0 to 6 inclusive,n represents an integer of from 0 to 6 inclusive,R1, and R2 represent a group selected from hydrogen, alkyl, aryl and arylalkyl, or R1+R2 form together with nitrogen carrying them saturated, monocyclic, or bicyclic system,X represents a group selected from oxygen, sulphur, a group —CH═CH—, methylene, a group of formula —HC═N—O— and a group of formula —O—CH2—CH═CH—, in which groups oxygen is linked to Y of the compounds of formula (I),Y represents a group selected from aryl, heteroaryl, arylalkyl, heteroarylalkyl, —C(O)-A, and —C(S)-A,A represents a group selected from alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and NR3R4 wherein R3, and R4 represent a group selected from hydrogen, alkyl, aryl, and arylalkyl, or R3+R4 form together with nitrogen carrying them monocyclic, or bicyclic (C3-C10) system,its isomers and addition salts thereof with a pharmaceutically-acceptable acid or base, and medicinal products containing the same which are useful as specific nicotinic ligand of α4β2 receptors.

The present invention pertains to the use of engineered variants of enzyme CYP102A, also known as P450-BM3, for cyclopropanation of olefins containing electron-withdrawing groups. One exemplary enzyme variant, referred to as BM3-HStar, contains five mutations away from wild-type P450-BM3, and demonstrates high activity towards cyclopropanation of olefinic substrates using ethyldiazoacetate (EDA) and other carbene transfer reagents. Products of these reactions are potential precursors of levomilnacipran derivatives, a class of compounds that have been shown to be selective inhibitors of monoamine transporters. In addition, cyclopropanation reactions with the P450-BM3 enzyme variants of the invention can be conducted in whole cells expressing the enzyme variants and can proceed under aerobic conditions.

An abscisic acid (1) is a plant hormone widely existing in a plant and has important physiological function, however, the application range is limited by the high-speed photo-isomerization characteristics. A bioisosteres cis 2, 3-cyclopropanated abscisic acid analogue of the abscisic acid is compounded through 2, 3-cyclopropanation, and the photostability is four times as that of the abscisic acid.

The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

The invention discloses a method and a device for continuously synthesizing cyclopropane compounds. The method comprises the following steps of: continuously carrying out a synthesis reaction of a diazomethane precursor in a first reactor, flowing a reaction product of the first reactor into a separator for layering, overflowing an organic phase obtained by layering into a second reactor, continuously consuming the diazomethane precursor in the second reactor to prepare diazomethane, and carrying out an electron-rich mono-olefin cyclopropanation reaction in situ to obtain the cyclopropane compounds. The method can realize automatic control, reduce the transfer of high-risk materials, avoid the risk of pipeline transfer of a diazomethane solution, and effectively improve the production safety, also has simple equipment, can save equipment investment, and can safely and quantitatively realize simultaneous diazomethane generation and olefin cyclopropanation reaction.

This invention provides improved methods for the derivatization and solubilization of fullerenes, which are particularly useful for those fullerenes that are normally insoluble and which are specifically applied, among others, to endohedral fullerenes, including endohedral metallofullerenes; empty fullerenes, including small-bandgap fullerenes and other insoluble fullerenes and to very high molecular weight fullerenic materials generated in fullerenic soot, including giant fullerenes, fullerenic polymers, carbon nanotubes and metal-carbon nanoencapsulates. More specifically the invention relates to improved methods for cyclopropanation of fullerenes. Specific reaction conditions are provided which allow for cyclopropanation reactions to be successfully performed for the first time on insoluble classes of fullerenes. Also provided is a method for purification of one or more fullerenes from a fullerenic material containing the one or more fullerenes in addition to non-fullerenic carbonaceous material, particularly amorphous carbonaceous material, by derivatizing one or more fullerenes using the methods of the invention and separating soluble derivatizes fullerenes from insoluble materials.

The invention discloses a method for preparing (1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. The method comprises the following steps: carrying out a Fuke acyl reaction on 3,4-difluorobromobenzene (compound 2) which serves as a raw material and chloroacetyl chloride under conditions of lewis acid and certain temperature to obtain a compound 3; carrying out stereoselective reduction to obtain a compound 4; carrying out cyclization, olefination, hydrolyzation and debromination to obtain a compound 8; and preparing amide, and carrying out Hoffmann elimination to obtain a target compound 1. According to the method, the traditional preparation process is improved, the (1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine can be effectively, simply and conveniently prepared, the total yield is relatively high, the stereoselection is relatively high, and the intermediate in each step is easily purified and stored. The reaction formula in the method is as shown in the specification.

The present invention provides methods for catalyzing the conversion of an olefin to any compound containing one or more cyclopropane functional groups using heme enzymes. In certain aspects, the present invention provides a method for producing a cyclopropanation product comprising providing an olefinic substrate, a diazo reagent, and a heme enzyme; and admixing the components in a reaction for a time sufficient to produce a cyclopropanation product. In other aspects, the present invention provides heme enzymes including variants and fragments thereof that are capable of carrying out in vivo and in vitro olefin cyclopropanation reactions. Expression vectors and host cells expressing the heme enzymes are also provided by the present invention.

The invention discloses a method for preparing 6beta,7beta-methylene-steride-3beta,5beta-diol, comprising the following steps of: preparing steride-4,6-dien-3beta-ol by using steride-4,6-dien-3beta-one as the raw material through a reductive reaction; preparing 4beta,5beta-epoxy steride-6-alkenyl-3beta-ol by the steride-4,6-dien-3beta-ol through epoxidation; preparing the intermediate steride-6-alkenyl-3beta,5beta-diol by the 4beta,5beta-epoxy steride-6-alkenyl-3beta-ol through a reductive ring opening reaction, and preparing the aimed compound 6beta,7beta-methylene-steride-3beta,5beta-diol by the intermediate through cyclopropanation reaction addition or directly preparing the aimed compound 6beta,7beta-methylene-steride-3beta,5beta-diol by the 4beta,5beta-epoxy steride-6-alkenyl-3beta-ol through cyclopropanation reaction. The invention has the advantages of low cost and easy availability of raw material, easy preparation of 4beta,5beta-epoxy steride-6-alkenyl-3beta-ol, high stereoselectivity for constructing 6beta,7beta-methylene structural unit, less reaction steps, simple operation and high yield, therefore, the method is suitable for industrialized production.

This invention relates to process for synthesizing S-(+)-2,2-dimethyl cyclopropane formyl amide, using penteneic acid as main raw material, after procedures of: esterification, cyclopropanization, hydrolyzation, acylation, salifying, partial crystallization and ammonolysis. advantages are: short reaction time, mild reaction condition, simple process, total yield is more than 15%, ee is larger than 95.6%.

A preparation method of 2-(o-hydroxyphenyl)cyclopropane-1-carboxylic acid is provided. With o-alkoxy cinnamic acid as a raw material, 2-(o-alkoxyphenyl)cyclopropane-1,1-ethyl dicarboxylate is obtained through pyrolysis decarboxylation, halogen addition and cyclopropanation, and then the novel tobacco spice 2-(o-hydroxyphenyl)cyclopropane-1-carboxylic acid is prepared through deestering, hydrolysis, demethylation and other steps. The raw material and reagents in the route are all commercial products, so that the raw material is easy to obtain; the reaction steps are all classic organic reactions, especially the cyclopropanation step avoids the use of expensive trimethylsulfoxonium halogen (TMSOX, wherein X is Cl, Br or I) reagents, and thus the cost of production is significantly reduced. Through process optimization, the overall yield of the reaction reaches 53%. The method has the advantages of simple operation, high synthesis yield, low costs of the raw material and the reagents, easy scale production and the like. The 2-(o-hydroxyphenyl)cyclopropane-1-carboxylic acid prepared by the method is mainly used in spice and essence industries.

The invention belongs to the field of synthesis of a metal complex, and particularly relates to a metal complex of a novel double piperidine derivative with a symmetric structure. According to the complex, under the protection of nitrogen gas, salt of corresponding metal is added into a reaction bottle provided with a reflux condensing tube; methanol is used as a solvent; the salt and the solvent are stirred until the salt is dissolved to obtain clear solution; double piperidine ligand is added and is heated under stirring until reflux occurs; after the double piperidine ligand is not available in the solution to be reacted, the solution is cooled to room temperature; the solvent is removed under reduced pressure; and residues are recrystallized to obtain the metal complex of the corresponding double piperidine derivative. The metal complex of the double piperidine derivative shows better catalytic performance in catalytic reaction such as epoxidation of olefin, asymmetric epoxidation of olefin, asymmetric addition of benzaldehyde and diethyl zinc and cyclopropanation of styrene.

A chiral ligand represented by the formula and its enantiomer: wherein A, X, Y and Z are as defined in the specification is provided. Also provided is a process of making the chiral ligands and catalysts prepared from these ligands and a transition metal, a salt thereof or a complex thereof. In addition, a method of preparing an asymmetric compound by a transition metal catalyzed asymmetric reaction, such as, hydrogenation, hydride transfer reaction, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydrocarboxylation, allylic alkylation, epoxidation, cyclopropanation, Diels-Alder reaction, Aldol reaction, ene reaction, Heck reaction and Michael addition is provided.

The invention discloses a method for preparing a ticagrelor intermediate. The method comprises the following steps: taking o-difluorobenzene and chloroacetyl chloride as initial raw materials, carrying out an F-K reaction, a bio-enzyme fermentation technology asymmetric reduction reaction, a ring-closure reaction and a cyclopropanation reaction, so as to obtain the key intermediate (1R, 2R)-2-(3,4-difluorophenyl) cyanocyclopropane carboxylate of the ticagrelor at high yield, high enantioselectivity and high purity. The method can realize industrialized production. The method is low in energy consumption, less in pollution, green, clean, high in yield and high in purity, the cost is reduced, the product quality is stable, and the method is suitable for large-scale stable industrial production.

Chiral ligands and metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The metal complexes according to the present invention are useful as catalysts in asymmetric reactions, such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition; epoxidation, kinetic resolution and [m+n] cycloaddition. Processes for the preparation of the ligands are also described.