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d-Penicillamine is used against a variety of diseases. For many years it has been successful in treating Wilson's disease, cystinuria and heavy-metal poisonings. It also proved to be effective against rheumatoid arthritis, scleroderma, chronic active hepatitis, pulmonary fibrosis and multiple sclerosis. However, the use of d-penicillamine is still limited owing to the frequent occurrence of considerable, though generally reversible, side effects. This article deals with the history of d-penicillamine as well as the methods of its synthesis, its pharmacokinetics, effects and side effects. In addition, the significance of the stereo isomeric l-penicillamine is discussed.
- Lodemann, Edgar
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Read Online
- Organic total synthesis method of D-penicillamine
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The invention discloses an organic total synthesis method of D-penicillamine, which comprises the following steps: carrying out Grignard reaction on a derivative of Lserine ester and a methyl Grignardreagent to obtain a first intermediate; carrying out oxidation reaction on the first intermediate and an oxidizing agent to obtain a second intermediate; carrying out sulfonylation reaction on the second intermediate and a sulfonylation reagent to obtain a third intermediate; carrying out thiolation reaction on the third intermediate and a vulcanization reagent to obtain a fourth intermediate; and carrying out hydrolysis reaction on the fourth intermediate to obtain the D-penicillamine. The initial raw materials are cheap and easy to obtain, particularly, cheap, easy-to-obtain and high-optical-purity Lserine ester derivatives can be used as the raw materials, the whole synthetic route for preparing the Dapenem is a new organic total synthesis process route, the process is simple, the reaction condition requirement is low, no toxin is left, and the safety performance is good; the product yield and the optical purity are high; and large-scale production is easy to realize.
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Paragraph 0023; 0036-0037; 0046-0047
(2020/11/23)
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- A NOVEL, FEASIBLE AND COST EFFECTIVE PROCESS FOR THE MANUFACTURE OF D – PENICILLAMINE
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Disclosed herein is a novel synthesis for the manufacture of D Penicillamine via novel chiral auxiliaries as intermediate compounds. The process comprises conversion of D Camphoric acid into an amido ester by reacting it with glycine methyl ester hydrochloride followed by conversion into its bis-acid by reacting with a suitable base. The bis-acid is further converted into its bis- oxazolone which is condensed with acetone in presence of base to obtain intermediate 5 followed by reaction with sulphur transfer agent and subsequent hydrolysis to obtain D Penicillamine.
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Page/Page column 13
(2018/08/12)
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- Immunomodulatory peptides
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The invention relates to peptides derivatized with a hydrophilic polymer which, in some embodiments, bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used in some embodiments, for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates, in further embodiments, to methods of using and methods of making the peptides of the invention.
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- Glycation Cross-link Breakers to Increase Resistance to Enzymatic Degradation
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The present invention relates to a method to treat a grafts, implant, scaffold, and constructs, including allografts, xenografts, autografts, and prosthetics comprising collagen, with an inhibitor of collagen cross-links and/or advanced glycation endproducts (AGE), in order to alleviate the mechanical weakness induced by the cross-links The invention also provides for kits for use in the operating theater during autograft, allograft or xenograft procedures, or for preparing allograft, xenografts or prosthetics that have not been already treated prior to packaging. The kit comprises a first agent or agents that inhibit collagen cross-links and/or advanced glycation endproducts, instructions for use, optionally a wash or rinse agent, and a device for containing the graft and first agent.
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- Novel Fluorescent Dyes and Uses Thereof
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The present invention provides fluorescent dyes that are based on firefly luciferin structure. These dyes are optimally excited at shorter wavelengths and have Stokes shift of at least 50 nm. The fluorescent dyes of the invention are useful for preparation of dye-conjugates, which can be used in detection of an analyte in a sample.
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- Pharmaceutical compounds for treating copd
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Use of an MPO inhibitor for the treatment of COPD.
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- Enantiomeric analysis of pharmaceutical compounds by Ion/molecule reactions
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Protonated complexes involving cyclodextrin hosts and guest compounds that are pharmacologically important are produced in the gas phase and reacted with a gaseous amine. The guest is exchanged to produce a new protonated complex with the amine. The reaction is enantioselective and is used to develop a method for determining enantiomeric excess using only mass spectrometry. The pharmaceutical compounds include DOPA, amphetamine, ephedrine, and penicillamine. The presence of more than one reacting species is observed with DOPA and penicillamine. Molecular dynamics calculations are used to understand the nature of the interactions and the possible source of the variations in the reactivities.
- Grigorean,Lebrilla
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p. 1684 - 1691
(2007/10/03)
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- Peptides with an insulin-like action
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Peptides with an insulin-like action, of formula I: STR1 in which G is a hydrogen atom, an amino add residue, or a monosubstituted or polysubstituted amino acid; D is an amino acid residue, a phosphoamino acid residue, a monosaccharide residue, or a covalent bond; E is --NH--(CH2)n --NR52, a glycerol residue, or --NH--(CH2)p --R6 --R7 ; R1 is (C1 -C4)-alkyl or =O; R2 is a sulfhydryl protecting group, (C1 -C3)-alkyl, or a hydrogen atom; R3 and R4, independently of one another, are a hydrogen atom or methyl; R5, each being identical or different, is a hydrogen atom, 1 to 6 monosaccharide residues, or 1 to 6 monosubstituted or polysubstituted monosaccharide residues; R6 is O PO4 H, PO2 H, NHCOO, S or OCOO; R7 is a hydrogen atom, 1 to 6 monosaccharide residues, or 1 to 6 monosubstituted or polysubstituted monosaccharide residues; w is an integer 1 or 2; their preparation and use for treatment of diabetes mellitus or insulin-independent diabetes.
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- PREPARATION OF D-PENICILLAMINE. REACTION OF PENILLOIC ACID, PENICILLOIC ACID α-AMIDES AND BENZYLPENICILLIN WITH N,N'-DIPHENYLETHYLENEDIAMINE
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Reaction of benzylpenilloic acid (1) with N,N'-diphenylethylenediamine (2) in mixture of water, acetic acid and toluene under reflux yielded D-penicillamine (4).In a similar way, 4 was also obtained from benzyl- and phenoxymethylpenicilloic acid α-amides (6a-f) and benzylpenicillin potassium salt (13).The structures of the byproducts formed in these reactions were also determined.
- Ogawa, Toshihisa,Tomisawa, Kazuyuki,Sota, Kaoru
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p. 2815 - 2824
(2007/10/02)
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- Process for the ring cleavage of 2-isopropyl-5,5-dimethylthiazolidines substituted in the 4-position
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A process for the ring cleavage of 2-isopropyl-5,5-dimethylthiazolidines in aqueous acid medium at elevated temperature. Whenever the five ring in the 4-position is substituted by a carboxyl group, penicillamine is the resultant product.
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- A FACILE PREPARATION OF D-PENICILLAMINE. REACTION OF BENZYLPENILLOIC ACID WITH ARYLAMINES
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The preparation of D-penicillamine (3) was achieved by the reaction of benzylpenilloic acid (1) with arylamines (2, 7, 13, 15) through ring fission of thiazolidine.The structures of the by-products formed in these reactions were determined.
- Ogawa, Toshihisa,Tomisawa, Kazuyuki,Sota, Kaoru
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p. 1421 - 1430
(2007/10/02)
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- 60CO-irradiation as an alternate method for sterilization of Penicillin G, neomycin, novobiocin, and dihydrostreptomycin
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The effects of the use of 60Co-irradiation to sterilize antibiotics were evaluated. The antibiotic powders were only occasionally contaminated with microorganisms. The D-values of the products and environmental isolates were 0.028, 0.027, 0.015, 0.046, 0.15, 0.018, and 0.19 Mrads for Aspergillus species (UC 7297, 7298), A. fumigatus (UC 7299), Rhodotorula species (UC 7300), Penicillium oxalicum (UC 7269), Pseudomonas maltophilia (UC 6855), and a biological indicator microorganism, Bacillus pumilus spores (ATCC 27142). An irradiation dose of 1.14 Mrads, therefore, was sufficient to achieve a six-log cycle destruction of B. pumilus spores. Based on the bioburden data, a minimum irradiation dose of 1.05 Mrads was calculated to be sufficient to obtain a 10-6 probability of sterilizing the most radioresistant isolate, Pen. oxalicum. To determine the radiolytic degradation scheme and the stability of the antibiotics following irradiation, high-performance liquid chromatographic (HPLC) methods were developed. The resulting rates of degradation for the antibiotics were 0.6, 1.2, 2.3, and 0.95%/Mrad for penicillin G, neomycin, novobiocin, and dihydrostreptomycin, respectively. Furthermore, radiolytic degradation pathways for the antibiotics were identified and found to be similar to those commonly encountered when antibiotics are subjected to acidic, basic, hydrolytic, or oxidative treatments. No radiolytic compounds unique to 60Co-irradiation were found.
- Tsuji,Rahn,Steindler
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- Method for preparing d-penicillamine and salts thereof
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D-Penicillamine and salts thereof may be prepared by reacting certain aryl amines with 4-thiazolidinecarboxylic acid compounds obtained by splitting the β-lactam ring of penicillin derivatives such as benzylpenicillin or phenoxymethylpenicillin.
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- Process of preparing penicillamine
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Improvements in the process of preparing penicillamine or a homolog thereof by reacting an α-carbon atom branched aldehyde, sulfur and ammonia to form a thiazoline-Δ3, reacting the thiazoline-Δ3 with anhydrous hydrogen cyanide to form a thiazolidine-4-carbonitrile, hydrolyzing the nitrile to form a mixture of the salt of the thiazolidine-4-carboxylic acid and ammonium salts, separating off the ammonium salts and hydrolytically decomposing the thiazolidine-4-carboxylic acid, wherein under the action of a mineral acid the thiazolidine-4-carbonitrile is in the first stage converted at low temperatures into the salt of the thiazolidine-4-carbonamide and then at higher temperatures converted into the salt of the thiazolidine-4-carboxylic acid.
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- Resolution of D,L-protected-penicillamine
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The D-form of an optically active protected penicillamine is prepared by treating a solution of D,L protected penicillamine of the formula: EQU1 wherein Ac is formyl, and R1 and R2 are both methyl or are joined together to form the pentamethylene group.
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- Process for the preparation of D(-)-penicillamine and salts thereof
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D(-)-Penicillamine and salts thereof may be prepared by reacting a 6-amino or blocked 6-amino penicillin e.g. penicillin G or penicillin V, or a salt thereof, with a hydrazine having two --NH-groups, or a salt or solvate thereof.
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- Process for the resolution of D,L-penicillamine and salts formed during said process
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D,L-penicillamine is separated into its antipodes employing optically active threo-1-(p-nitrophenyl)-2-aminopropanediol-1,3.
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- Process of making penicillamine
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Penicillamine or a homolog thereof is obtained by reacting a 2-disubstituted-5,5-alkyl-thiazolidine nitrile, alkyl having 1 to 6 carbon atoms, with a mineral acid in a two-stage proceeding wherein in the first stage relatively low temperatures and a relatively high concentration of the mineral acid are employed while in the second stage the concentration of the acid is relatively low and the temperatures are relatively high, the term "relatively" referring to the relationship of said two stages of the reaction with mineral acid.
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- Method of producing penicillamine
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This invention relates to the production of penicillamine and acid addition salts of penicillamine through the production from penilloic acid or penicilloic acid formed by hydrolytic decomposition of a penicillin of penicillamine-mercuric-mercaptide which can be easily decomposed by means of hydrogen sulfide to penicillamine. The penicillamine-mercuric-mercaptide is formed as a crystalline precipitate by reaction of the penicilloic acid or penilloic acid with a mercuric salt in a ratio of 1:0.5 in a medium of a water miscible organic solvent and the precipitated penicillamine-mercuric-mercaptide after separation from the reaction medium is decomposed to the penicillamine.
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- Optically active salt of protected D-penicillamine and L-lysine
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D,L-penicillamine is converted to D-penicillamine with the aid of L-lysine.
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- Resolution process and salt of protected D-penicillamine and L-pseudonorephedrine
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D,L-penicillamine is converted to D-penicillamine with the aid of 1-pseudonorephedrine.
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