166 results about "Chiral auxiliary" patented technology

The invention provides a stereselective synthesis method for a lipid-lowering drug ezetimibe shown in formula I. The method comprises the following steps: a, P-fluorobenzoyl butyric acid shown in formula II reacts with a chiral auxiliary shown in formula III to obtain ketone shown in formula IV; b, under the existence of a chiral catalyst, the ketone shown in formula IV is reduced to chiral alcohol shown in formula V; c, chiral alcohol shown in formula V reacts with a silicyl protective agent to obtain a protected compound shown in formula VI, and then the compound shown in formula VI and imine shown in formula VII are subjected to addition and protecting groups are removed, so that a compound shown in formula VIII and a diastereomer thereof shown in formula IX are obtained, and through recrystallization with an appropriate solvent, an optically pure compound shown in formula VIII is obtained; d, the compound shown in formula VIII is protected with an acylation reagent, so that a compound shown in formula X is obtained, and amide shown in formula X is cyclized with a fluorinion catalyst, so that protected lactam shown in formula XI is obtained; then protecting groups are removed, and the ezetimibe shown in formula I is obtained.

The disclosed and claimed compounds are chiral auxiliaries useful for efficiently producing a phosphorus atom-modified nucleic acid derivative with high stereoregularity. The disclosed and claimed compounds include those represented by the following formula (I) or formula (XI) for introducing the chiral auxiliaries.

The invention relates to an asymmetric hydrogen transfer synthesis method for (R,R)-formoterol, and relates to a novel method for synthesizing an optical pure beta 2-adrenoreceptor excitant, namely formoterol. The method comprises: firstly, taking 4-hydroxyl-3 nitroacetophenone as a raw material, using benzyl groups to protect phenolic hydroxyl groups, and obtaining alpha-bromo keto after bromination; secondly, taking (S,S)-Rh-PEG-BsDPEN as a catalyst and formic acid and derivatives of the formic acid as hydrogen sources, and synthesizing chiral alcohol intermediate by an asymmetric hydrogen transfer method; thirdly, using (R)-alpha-methyl phenylethylamine and methoxyl phenylacetone to generate imine compounds, and obtaining chiral amine intermediate through hydrogenation reduction under the catalysis of Pt / C; and fourthly, reacting and coupling the chiral alcohol intermediate and the chiral amine intermediate, removing protective groups, and obtaining the (R,R)-formoterol. The invention uses the asymmetric hydrogen transfer method and a chiral auxiliary reagent to synthesize the (R,R)-formoterol, and has high yield and good ee value. Compared with a method for synthesizing chiral formoterol through chemical splitting, the method has the advantages of high total yield, mild reaction conditions, low cost and so on, and is favorable for industrial production.

The invention provides a preparation midbody for Ezetimibe which is shown in a general formula I, wherein PG is an acetyl group, a T-butyloxycarbonyl group, a benzyl group, a benzyloxycarbonyl group, a trityl group, a trimethylsilyl group or a diphenylmethyl group silicon group. The invention further provides a preparation method of the midbody I, and the application for preparing the medicine Ezetimibe. The method for preparing the Ezetimibe by adopting the compounds shown in the general formula I is different from the method in the conventional document, the newer chirality assistant (S)-4-(2-chlorphenyl)-2-oxazolone is adopted, the productive rate reaches 91%, and the optical purity reaches 100%, so that the productive rate and the optical purity are higher than those of the previously applied (S)-4-phenyl-2-oxazolone. Besides, the selected chirality assistant (S)-4-(2-chlorphenyl)-2- oxazolone can be conveniently prepared by the original commercialized ((S)-2-chlorobenzene glycine potassium).

The invention provides a method for producing S-(-)-amlodipine besylate. The method comprises the following steps: 1, reacting R,S-amlodipine with the structural formula represented by formula I and a resolving agent which are treated as raw materials in a mixed solution of water and an organic solvent to obtain an intermediate 1; and 2, directly reacting the intermediate 1 with benzenesulfonic acid in the mixed solution of water and the organic solvent to obtain the S-(-)-amlodipine besylate, wherein the resolving agent in step 1 is selected from L-tartrate or D-tartrate. The method of the invention, which adopts cheap tartrate as the resolving agent and certain proportions of water and the organic solvent as chiral assistants, allows the optical purity of the obtained S-(-)-amlodipine besylate to reach 99.9%, the S-(-)-amlodipine besylate to be obtained by directly reacting the intermediate 1 with benzenesulfonic acid without hydrolysis, and the yield and the crystal form to be verygood, so the method has a good industrial application prospect.

The invention relates to an asymmetric synthesis method of (R,R)-formoterol tartrate, which comprises the following steps: by taking (S,S)-CsDPEN and transition metal complex as a catalyst, performing asymmetric hydrogen transfer reaction on alpha-bromoketone used as a raw material, thus obtaining a chiral alcohol intermediate compound; performing reaction steps of nitro-reduction, formylation, cyclization and the like, thus obtaining a key intermediate compound FM 1; by taking Pt / C as a catalyst and alpha-methylphenylethylamine as a chiral assistant, synthesizing an intermediate compound FM 2-3; performing tartaric acid salification, ionization and alpha-methylphenethyl removal, and reacting with benzaldehyde, thus preparing a chiral amine intermediate compound FM 2; reacting and coupling the two key intermediate compounds, and performing protective group removal to obtain (R,R)-formoterol FM 4; and performing tartaric acid salification on the FM 4, thus preparing the target product (R,R)-formoterol tartrate FM 5. According to the invention, the (R,R)-formoterol is synthesized through an asymmetric hydrogen transfer method by means of the chiral assistant, and high yield and favorable ee value are achieved. Compared with a chemical resolution method for synthesizing chiral formoterol, the method provided by the invention has the advantages of high overall yield, mild reaction conditions, low cost and the like, thereby being beneficial to industrial production.

The present invention discloses a chiral coordination polymer crystal and a preparation method thereof, (1) the chiral coordination polymer crystal has the characteristics of simple preparation, and single chiral structure; (2) ligand 3-(3-carboxylic)-4-allyloxy-azo phenylacetic acid exists in general in a trans stable configuration, and has a special structure, a specific spiral mode is used for coordination reaction in the coordination reaction, a coordination polymer can be obtained by the specific spiral mode under normal temperature liquid phase conditions from the ligand and a metal ion, and preferably, when the metal ion is Zn<2+>, a single chiral crystal structure can be obtained; (3) chiral auxiliaries and chiral ligands are not needed in the preparation method of the chiral coordination polymer crystal, a single chiral spiral can be realized by lattice orientation special selectivity, and the single chiral crystal can be formed, and has potential application in efficient chiral separation and chiral recognition and other aspects.

The invention discloses a 1-deoxidized nojiri toxin derivative and a relative preparation method, which uses natural cheap D-glucose as material to synthesize dicarbonyl-D-glucose, and processes enamine double-reduction reaction on the dicarbonyl-D-glucose and amine, to obtain 1-deoxidized nojiri toxin derivative with high yield and spatial selectivity. The derivative can be used as intermediate and chiral auxiliary of organic synthesis or drug synthesis, to chirally synthesize organic or drug. The invention further discloses a full synthesis process of 1-deoxidized nojiri toxin derivative, with spatial control, simple operation, mild condition, high yield and industrialization suitability.

The invention discloses a synthetic method of ezetimibe, and an intermediate used in the synthetic method. According to the synthetic method, allyl amination of Morita-Baylis-Hillman adducts is performed so as to realized production of a chiral beta-aromatic amido alpha-methylene carboxylic acid derivative with high activity and selectivity, and the chiral ezetimibe synthetic intermediate is obtained via simple conversion reaction; and chiral medicament ezetimibe can be synthesized further. According to the synthetic method, chirality of ezetimibe is realized via chiral catalysis, so that the use of chiral auxiliary base oxazolidinone is avoided, cost is low, and the synthetic method is friendly to the environment.

The invention discloses a method for preparing bortezomib with (one)-cypress camphor serving as a chiral auxiliary reagent. The technological process includes that the (one)-cypress camphor and boronic acids in an organic solvent form boronic acid-(one)-cypress camphor esters; the boronic acid-(one)-cypress camphor esters are condensed and rearranged at a low temperature to obtain 2-chloro isoamyl boronic acid-(one)-cypress camphor esters; the 2-chloro isoamyl boronic acid-(one)-cypress camphor esters are aminated by lithium bis (trimethylsilyl) amide and removed protecting groups to obtain (one)-cypress camphor-(R)-1-amino-3-isobutyl-borate trifluoroacetic acid salt; the (one)-cypress camphor-(R)-1-amino-3-isobutyl-borate trifluoroacetic acid salt and pyrazine formyl-L-phenylalanine react under the existence of a condensing agent to generate bortezomib-(one)-cypress camphor esters; and the bortezomib-(one)-cypress camphor esters are hydrolyzed to generate bortezomib monomers and further generate bortezomib tripolymers.

The invention discloses a preparation method of Niraprib of a PARP inhibitor and two key intermediates used in the preparation method. The preparation method comprises the following steps: taking 4-methyl alpha-bromophenylacetate and (S)-tert-butanesulfinyl amide as raw materials, and performing condensation, asymmetry alkylation, reduction and coupling on the raw materials, so as to obtain a keyintermediate compound 5; condensing and coupling the compound 5, so as to obtain a compound 6; hydrolyzing the compound 6 under the action of p-toluenesulfonic acid to remove a protecting group, so asto obtain a target product Niraprib. The preparation method has the beneficial effects that the conventional resolution and chiral source methods are overcome by introducing the asymmetry alkylationinduced chirality of a chiral auxiliary, so that the preparation method is simple in operation, mild in conditions, good in yield and relatively high in chemical purity and optical purity; in addition, key intermediates 5 and SM3 are condensed to form a target compound 1, so that the original patent is broken through, and the preparation method is suitable for industrial production.