- Preparing method of captopril isomer
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The invention provides a preparing method of a captopril isomer. The method includes the steps of resolving mixed 3-sulfanyl-2-methyl propionic acid into L-3-sulfanyl-2-methyl propionic acid, making L-3-sulfanyl-2-methyl propionic acid react with thionyl chloride to prepare L-3-sulfanyl-2-methylpropionyl chloride (L-acyl chloride for short), making L-acyl chloride react with L-proline or D-prolineto generate 1-(3-sulfanyl-2-methylpropionyl)-proline (free acid for short), and conducting hydrolysis deprotection on the free acid to prepare the isomer. The preparing method is good in resolving effect, the obtained isomer is high in optical purity, the resolving reaction time and temperature range is large, and control is easy.
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Paragraph 0020; 0026-0027; 0032; 0038-0039; 0044; 0050; 0051
(2019/04/26)
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- Structural basis of metallo-β-lactamase inhibition by captopril stereoisomers
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β-Lactams are the most successful antibacterials, but their effectiveness is threatened by resistance, most importantly by production of serine- and metallo-β-lactamases (MBLs). MBLs are of increasing concern because they catalyze the hydrolysis of almost all β-lactam antibiotics, including recent-generation carbapenems. Clinically useful serine-β-lactamase inhibitors have been developed, but such inhibitors are not available for MBLs. L-Captopril, which is used to treat hypertension via angiotensin-converting enzyme inhibition, has been reported to inhibit MBLs by chelating the active site zinc ions via its thiol(ate). We report systematic studies on B1 MBL inhibition by all four captopril stereoisomers. High-resolution crystal structures of three MBLs (IMP-1, BcII, and VIM-2) in complex with either the L- or D-captopril stereoisomer reveal correlations between the binding mode and inhibition potency. The results will be useful in the design of MBL inhibitors with the breadth of selectivity required for clinical application against carbapenem-resistant Enterobacteriaceae and other organisms causing MBL-mediated resistant infections.
- Brem, Jürgen,Van Berkel, Sander S.,Zollman, David,Lee, Sook Y.,Gileadi, Opher,McHugh, Peter J.,Walsh, Timothy R.,McDonough, Michael A.,Schofield, Christopher J.
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supporting information
p. 142 - 150
(2016/02/19)
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- Asymmetric induction in the conjugate addition of thioacetic acid to methacrylamides with chiral auxiliaries
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The conjugate addition of thioacetic acid to methacrylamides with chiral C2-symmetric trans-2,5-disubstituted pyrrolidines afforded the addition products in excellent stereoselectivities (>99% de) and good yields (80-90%). The high selectivity was attributed mainly to the steric effect of the chiral auxiliaries. The cyclic nature of the chiral auxiliaries seemed also important for both the stereoselectivity and the reaction rate. Acidic hydrolysis of the adduct containing (2R,5R)-bis(methoxymethyl)pyrrolidine gave (S)-3-mercapto-2-methylpropanoic acid, a key intermediate for captopril, in 98% ee and 96% yield. The chiral auxiliary was recovered in the demethylated form of N-Boc-(2R,3R)-bis(hydroxymethyl)pyrrolidine in 90% yield.
- Kim, Byung Hyun,Lee, Hee Bong,Hwang, Jae Kwang,Kim, Young Gyu
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p. 1215 - 1220
(2007/10/03)
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- A mild and efficient procedure for the preparation of acid chlorides from carboxylic acids
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Various carboxylic acids are converted into the corresponding acid chlorides by treatment with trichloroacetonitrile and triphenylphosphine in methylene chloride at room temperature. Aryl acids show higher reactivity than alkyl acids under the conditions.
- Jang, Doo Ok,Park, Doo Jin,Joonggon, Kim
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p. 5323 - 5326
(2007/10/03)
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- Thiazaspirane derivatives, process for their preparation, and medicaments
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Novel thiazaspirane derivatives of the general formula STR1 including salts thereof with physiologically acceptable acids and bases, processes for their preparation and medicaments containing them.
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- Angiotensin-Converting Enzyme Inhibitors. New Orally Active Antihypertensive (Mercaptoalkanoyl)- and glycine Derivatives
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A variety of N-substituted (mercaptoalkanoyl)- and glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo.The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds.A number of this compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model.One of the most active members of the series was (S)-N-cyclopentyl-N--2-methyl-1-oxopropyl>glycine (REV 3659-(S), pivopril).Structure-activity relationships are discussed.
- Suh, John T.,Skiles, Jerry W.,Williams, Bruce E.,Youssefyeh, Raymond D.,Jones, Howard,et al.
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