38results about How to "Reduce racemization" patented technology

The present invention provides an improved process for preparing β-D and β-L 2′-C-methyl-nucleosides and 2′-C-methyl-3′-O-ester nucleosides.

This invention provides an improved asymmetric process for the synthesis of duloxetine involving arylation of Compounds of Formula I.

In a first aspect, the present invention relates to a process for producing a stable, injectable solution with low content of noradrenaline, which includes dissolving noradrenaline and optionally an excipient in deoxygenated or degassed water, filtrating the resulting noradrenaline solution in a nitrogen current, distributing the solution in a nitrogen current, and sterilization, preferably hot. The invention further provides a stable, injectable solution with low content of noradrenaline, substantially free of anti-oxidizing and preservative agents, as well as uses thereof in the medical and pharmaceutical fields.

The present invention provides methods, apparatus and kits for synthesizing assembled peptides and proteins on a solid phase with sequential ligation of three or more unprotected peptide segments using chemoselective and mild ligation chemistries in aqueous solution. Also provided are methods of monitoring solid phase sequential ligation reactions using MALDI or electrospray ionization mass spectrometry of reaction products.

The present invention provides a process for producing a peptide thioester compound. The process involves: (A) forming a peptide by a solid-phase synthesis method using a resin modified with a linker represented by the formula (1) as a solid phase:wherein R1 represents C1-4 alkyl group, R2 represents hydrogen atom or C1-4 alkoxy group, and n represents an integer of 1 to 4; (B) cleaving a bond between the solid phase and the peptide with at least one acid selected from dilute hydrochloric acid, dilute sulfuric acid, formic acid, and acetic acid to produce a peptide having a carboxyl group at the C-terminus; and (C) reacting a thiol compound with the peptide at −100 to 0° C. in the presence of a condensing agent in a solvent.

The invention provides a solid phase method of secretin, which comprises the following steps: 1) selecting an appropriate solid phase carrier; 2) coupling amino acids one by one according to a solid phase synthetic method; 3) splitting for obtaining a crude peptide; 4) obtaining the secretin by purifying the crude peptide, wherein, the solid phase synthesis employs Fmoc-strategy, and false proline is used for replacing parts of serine in the peptide chain during the solid phase synthesis. The solid phase method of secretin provided by the invention has the advantages of simple operation, small impurity, easy purifying and high yield, and is beneficial to realization of industrialization.

The solid-phase synthesis method of octreotide acetate of the present invention belongs to the field of polypeptide synthesis. First, the acetalization product is bonded to a polymer resin; the bonded product is sequentially bonded to the protected amino acid residues and deprotected to obtain an octapeptide resin; the octapeptide is cut from the resin to make an aqueous solution, and Octreotide is made after natural oxidation in the air; glacial acetic acid is added to the octreotide aqueous solution and then freeze-dried to make octreotide acetate. The invention has simple synthesis process, easy operation, shortened process time, small reaction ratio, saved raw materials, reduced cost, improved yield and purity, fewer side reactions and by-products, convenient purification, and beneficial to mass production.

The invention discloses a synthesis method of active cyclic octapeptide Reniochalistatin E and an analogue thereof. A complete synthesis method of the cyclic octapeptide disclosed by the invention adopts a polypeptide solid phase synthesis method, and the synthesis time and purification processes are greatly shortened; in order to prevent the condition that hydrogen on tryptophan indole nitrogen possibly causes decrease of a connection rate and increase of by-products, tryptophan with protection of carbonyl tert-butyl (Boc) on indole is adopted as a raw material, and finally, after cyclizationis finished, a TFA / DCM solution with a high volume ratio is adopted for removing Boc protection to obtain a final product. Compared with traditional condensation reagents and cyclization reagents, condensation reagents DEPBT and DIEA and a cyclization reagent PyBOP adopted by the invention have the advantages of greatly reducing racemization caused by reaction processes and reducing toxicity hazards to the body of a user. The product obtained by the synthesis method provided by the invention is simple in synthesis process, low in raw material cost, mild in reaction condition, high in purity and easy to industrialize, and has broad market prospects.

The present invention discloses solid phase synthesis process of adrenal medullarin (27-52). The synthesis process includes the first solid phase Fmoc polypeptide synthesis to graft protective amino acid Fmoc-Ala-OH onto resin, connecting the rest protective amino acids successively, cutting down the synthesized coarse peptide with peptide cutting reagent, and final separating and purifying to obtain the adrenal medullarin (27-52) as the target peptide. The present invention has mild reaction condition, high reaction rate, less side reactions, easy purification, high yield, no corrosion to the equipment and no environmental pollution.

The invention relates to a method for separating L-glutamic acid and L-pyroglutamic acid from a glutamic acid refinement mother solution. The method comprises the following steps: 1) carrying out vacuum concentration on the glutamic acid refinement mother solution, cooling to crystallize, and centrifugating, wherein the solid is the L-glutamic acid crude product, and the liquid is for later use; 2) washing the L-glutamic acid crude product with water to obtain pure L-glutamic acid; and 3) heating the liquid obtained in the step 1), carrying out pressurized pyrogenic reaction, cooling, concentrating, cooling to crystallize, centrifugating, collecting the precipitate, adding water to a saturated state, recrystallizing, cooling, and carrying out centrifugal separation to obtain the L-pyroglutamic acid. The method is simple in technical process, and can well solve the problem of the separation technique for glutamic acid and pyroglutamic acid, thereby achieving the goals of enhancing the L-glutamic acid refinement yield and coproducing the L-pyroglutamic acid.

Disclosed herein is a method for preparing a hyaluronan-drug conjugate. The method uses the ethyl cyano(hydroxyimino)acetate / diisopropylcarbodiimide coupling system in a homogeneous reaction phase, which unexpectedly improves the substitution rate and substitution efficiency of hyaluronan-drug conjugates for various drugs.