- 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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Read Online
- Preparation method of L-penicillamine
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The invention discloses a preparation method of L-penicillamine, which comprises the following steps: protecting sulfydryl and amino in penicillamine by using acetone and ethyl formate to obtain Nformyl isopropyl penicillamine; then, conducting racemization on N-formyl isopropyl-D-apenem by adopting acetic acid or a mixed solution of acetic acid and methylbenzene to acquire N-formyl isopropyl-D and L-apenem; reacting N-formyl isopropyl-D, Lapenem and hydrochloric acid to prepare N-formyl isopropyl-D, L-apenem hydrochloride; dissociating N-formyl isopropyl-D and Lapenem hydrochloride in lower alcohol through organic alkali to obtain a dissociated racemate D and L-apenem; d, reacting the L-Penicillamine with a resolving agent L-tartaric acid to obtain L-Penicillamine. Ltartrate; carrying outsalt hydrolysis on the L-Penicillamine. L-tartrate by using organic alkali to obtain the L-Penicillamine. According to the preparation method disclosed by the invention, the used resolution reagent is low in price, the reaction condition is mild, the product yield is high, and feasibility is provided for industrial mass production of the L-Penicillamine.
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Paragraph 0042-0043; 0057-0058; 0059; 0067
(2021/03/18)
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- Determination of Absolute Rate Constants for the Reversible Hydrogen-atom Transfer between Thiyl Radicals and Alcohols or Ethers
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Absolute rate constants have been determined for the reversible hydrogen-transfer process R. + RSH ->/. by pulse radiolysis, mainly through direct observation of the RS. radical formation kinetics in water-RH (1:1, v/v) mixtures.The thiols investigated were penicillamine and glutathione; the RH hydrogen donors were methanol, ethanol, propan-1-ol, propan-2-ol, ethylene glycol, tetrahydrofuran and 1,4-dioxane with the abstracted hydrogen being located α to the hydroxy or alkoxy function.Rate constants for the forward reaction of the above equilibrium (in radiation biology referred to as 'repair' reaction) were typically of the order of 1E7-1E8 dm3 mol-1 s-1 while hydrogen abstraction from RH by thiyl radicals (reverse process) occurred with rate constants of the order of 1E3-1E4 dm3 mol-1 s-1.This yields equilibrium constants of the order of 1E4.Based on these data, standard reduction potentials could be evaluated for the R'R''C.OH/H(1+)//R'R''CHOH, R'R''CO/H(1+)//R'R''C.(OH) and R'R''CO//R'R''C.O(1-) couples from methanol, ethanol and propan-2-ol.Effective hydrogen-atom abstraction by RS. required activation by neighbouring groups of the C-H bond to be cleaved in RH.No such process was observed for the RS. reaction with -CH3 groups, e.g. in 2-methylpropan-2-ol.Several halogenated hydrocarbons, including some anaesthetics (e.g. halothane) and Fe(CN)6(3-) have been tested with respect to their ability to disturb the (CH3)2C.OH + RSH ->/. equilibrium through an irreversible electron-transfer reaction with the reducing α-hydroxyl radical, thereby drawing the equilibrium to the left-hand side.The respective efficiencies are found to be related to the electronegativities of the electron acceptors.The results are briefly discussed in terms of their biological relevance.
- Schoeneich, Christian,Asmus, Klaus-Dieter,Bonifacic, Marija
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p. 1923 - 1930
(2007/10/02)
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- High molecular weight prodrug derivatives of antiinflammatory drugs
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Compounds of the formula 1, PS - O - A - (CH2)n- B - D (1), wherein PS-O represents an alkoxide residue of any of the free hydroxy groups of a polysaccharide (PS-OH) compound with molecular weight (Mw) of from 40,000 to 5,000,000 selected from dextran, carboxymethyl dextran, diethylaminoethyl dextran, starch, hydroxyet-hyl starch, alginates, glycogen, pullullan, agarose, cellulose, chitosan, chitin and carrageenan,A is a carbonyl group or absent,n is zero or a positive integer from 1 to 14,B is oxygen, a carbonyl group, NR wherein R is hydrogen or lower alkyl, or B is absent, and, D is (i) a group of the formula:, R1 - CO - (11), wherein R1-CO- represents the acyl residue of a carboxylic acid drug (R1-COOH) used in the treatment of inflammatory disorders; or (ii) a group of the formula:, R2 - O - (12), wherein R2-O- refers to the C-21 alkoxide residue of a known antiinflammatory steroid (R2-OH) or an alkoxide residue of any other drug or medicament containing a hydroxy functional group used in the treatment of inflammatory disorders; with the proviso that when A is absent, n is 0, and B is absent, then R1-CO- is different from the acyl residue of acetylsalicylic acid;, and non-toxic pharmaceutically acceptable acid addition salts thereof;, and non-toxic pharmaceutically acceptable cation salts thereof. Such compounds are biolabile prodrugs providing controlled release and prolonged duration of action of the parent active antiinflamma-tory agents locally at the administration site after intra-articular, intra-muscular, subcutaneous or extra-dural application while at the same time being highly stable in aqueous solution in the pH range 3--5. After oral administration of such prodrugs the parent drug is liberated selectively in the terminal ileum and the colon over an extended period of time.
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