- Preparation method of 3-acetylthio-2-methylpropionic acid
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The invention discloses a preparation method of 3-acetylthio-2-methyl propionic acid. The preparation method comprises the following steps: carrying out a reaction on a compound (methacrylic acid) represented by a formula I and hydrogen halide to obtain a compound represented by a formula II, carrying out a reaction on the compound represented by the formula II and sodium hydrosulfide or sodium sulfide to obtain a compound represented by a formula III, and performing an acetylation reaction to obtain a compound represented by a formula IV (3-acetylthio-2-methylpropionic acid). The process forsynthesizing the 3-acetylthio-2-methyl propionic acid has the advantages of being low in cost, easy and convenient to operate, good in yield, environmentally friendly and suitable for industrial production.
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Paragraph 0080-0082
(2020/05/02)
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- Tetrahydroisoquinoline derivative and application thereof
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The invention belongs to the technical field of medicines, relates to a 2-{(2s)-1-[(2S)-3-ethanethioate-2-methyl propionyl] pyrrolidine-2-formamido}-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid methyl ester derivative and an application thereof, and in particular relates to a stereomer and a pharmaceutically acceptable salt of the compound. The general structural formula is as shown in the specification. The 2-{(2s)-1-[(2S)-3-ethanethioate-2-methyl propionyl] pyrrolidine-2-formamido}-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid methyl ester compound as well as pharmaceutically acceptable acid and additive salt of the compound can be combined with an existing medicine and can be individually used as an angiotensin-converting enzyme inhibitor to be applied to treatment of hypertension. Compared with the prior art, 6,7,8 side chains of a tetrahydroisoquinoline ring are obviously changed; the inhibition rate of the sample on angiotensin-converting enzyme is significantly improved; and the tetrahydroisoquinoline derivative has good application values and development and application prospects.
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Paragraph 0033; 0041
(2016/10/27)
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- SN2-type nucleophilic opening of β-thiolactones (thietan-2-ones) as a source of thioacids for coupling reactions
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β-Thiolactones monosubstituted in the 3-position by alkyl and carbamoyl groups undergo nucleophilic ring opening by arenethiolates through a process involving an SN2-type attack at the 4-position leading to 3-arylthiopropionates substituted in the 2-position. These thiocarboxylates can be trapped in situ by Mukaiyama's reagent or Sanger's reagent through a nucleophilic aromatic substitution process leading to highly activated thioesters that are then allowed to react further with primary or secondary amines leading, overall, to one-pot, three-component syntheses of 3-arylthiopropionamides carrying various substituents in the 2-position. Alternatively, the trapping combination of an electron deficient aryl halide and an amine may be replaced by a 2,4-dinitrobenzenesulfonamide, resulting in the formation of the same products overall with the incorporation of the latent amine in the sulfonamide into the final amide product. In another embodiment, the thiocarboxylate intermediate is allowed to react with a sulfonyl azide, resulting overall in N-arenesulfonyl 3-arylthiopropionamide derivatives.
- Crich, David,Sana, Kasinath
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scheme or table
p. 3389 - 3393
(2009/10/02)
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- Reactivity of isothiazolones and isothiazolone-1-oxides in the inhibition of the PCAF histone acetyltransferase
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Development of small molecule inhibitors of the histone acetyltransferase p300/CBP associated factor (PCAF) is relevant for oncology. The inhibition of the enzyme PCAF and proliferation of the cancer cell line HEP G2 by a series of 5-chloroisothiazolones was compared to a series of 5-chloroisothiazolone-1-oxides. The PCAF inhibitory potency of 5-chloroisothiazolones and 5-chloroisothiazolone-1-oxides is influenced by substitution in the 4-position. A study on the reactivity of the HAT inhibitors towards thiols and thiolates indicates that 5-chloroisothiazolones reacted quickly with propane-1-thiolate to provide many products, whereas 5-chloroisothiazolone-1-oxides provide only one defined product. Growth inhibition studies indicate that 5-chloroisothiazolones inhibit proliferation of HEP G2 cells at concentrations between 8.6 and 24 μM, whereas 5-chloroisothiazolone-1-oxides required higher concentrations or showed no inhibition.
- Ghizzoni, Massimo,Haisma, Hidde J.,Dekker, Frank J.
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scheme or table
p. 4855 - 4861
(2010/01/16)
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- Optical resolution of DL-3-acetylthio-2-methylpropionic acid using L-(+)-2-aminobutanol as resolving agent
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This invention refers to a new process for the preparation of D-(-)-3-acetylthio-2-methylpropionic acid, an important intermediate in the synthesis of the antihypertensive Captopril, consisting of the resolution of the racemic mixture of said acid through formation of the mixture of the diastereomeric salts thereof, in an appropriate solvent, with the low molecular weight L-(+)-2-aminobutanol as a base, selective crystallization of the diastereomeric salt of D-(-)-3-acetylthio-2-methylpropionic acid with L-(+)-2-aminobutanol and release of the D-(-)-3-acetylthio-2-methylpropionic acid through displacement of the base with a stronger acid.
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- Process Conditions for Production of D-β-Acetylthioisobutyric Acid from Methyl DL-β-Acetylthioisobutyrate with the Cells of Pseudomonas putida MR-2068
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The process conditions concerned with the production of D-β-acetylthioisobutyric acid were investigated.Methyl DL-β-acetylthioisobutyrate as an enzyme substrate was produced from methyl methacrylate in 96.6percent yield by allowing 1.0 mol of methyl methacrylate to react with 1.6 mol of thioacetic acid at 80 deg C for 6 h.Through the study of hydrolytic reaction of methyl DL-β-acetylthioisobutyrate with the cells of Pseudomonas putida MR-2068, it was found that D-β-acetylthioisobutyric acid having more than 98percent (e. e.) optical purity was obtained when the reaction was done below pH 7.5 and below 50 deg C.For example, 10percent (w/v) methyl DL-β-acetylthioisobutyrate in the reaction mixture was asymmetrically hydrolyzed by 0.2percent (w/v) cells at 45 deg C at pH 7.0 for 18 h to give DAT having 98.2percent (e. e.) optical purity in 49.7percent yield.To prevent the decomposition and racemization of D-β-acetylthioisobutyric acid in the purification process, the use of a thin-film distillation apparatus for a continuous distillation was proposed to be an effective purification method.
- Sakimae, Akihiro,Ozaki, Eiji,Toyama, Hiroko,Ohsuga, Naoto,Numazawa, Ryozo,et al.
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p. 782 - 786
(2007/10/02)
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- Optical resolution of DL-3-acylthio-2-methylpropanoic acid
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An optically active amine compound and a method for preparing same are provided which compound has the structure STR1 in the form of its R-(+) enantiomer or S-(-) enantiomer, wherein R and R1 are independently H, lower alkyl or halogen, R2 is H or lower alkyl and R3 is lower alkyl, the optically active amine is useful in the optical resolution of DL-3-acylthio-2-methylpropanoic acid wherein acyl is acetyl or benzoyl. The optically active D-(+)-3-acylthio-2-methylpropanoic acids are used as intermediated for preparing antihypertensive agents, such as captopril.
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- ORALLY EFFECTIVE ANTI-HYPERTENSIVE AGENTS
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Novel thiolester compounds are disclosed which are orally effective angiotensin converting enzyme inhibitors useful in the treatment of mammalian hypertension. They have the formula, EQU1 wherein Z denotes-B-A 2, R 1 is H or an acyl group, A 1 is a carboxylic acid containing at least one amino or imino-N-, A 2 is a carboxylic acid containing at least one amino or imino-N-or a lower alkyl ester or amide thereof, B is a 2-4 carbon backbone chain in mercapto linkage to S which includes a carbonyl or sulfonyl group joined in carboxamido or sulfonamido linkage, respectively, to A 2. Preferably A 2 includes a 4-6 membered C-N ring or a 5 membered ring of one N, one S and 3 C atoms.
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- Anti-hypertensive agents
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Novel inhibitors of angiotensin converting enzyme having the general formula R--A--S--Z are disclosed as potent inhibitors of angiotensin converting enzyme and are useful anti-hypertensive agents.
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- Optically active N-substituted phenylalaninols and use thereof
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Optically active N-substituted phenylalaninols of the formula (I): STR1 wherein R is isopropyl, 1-ethylpropyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylbenzyl, 4-methoxybenzyl, or 3,4-methylenedioxybenzyl; and acid addition salts thereof which are useful as a resolving agent, and a process for preparing D-3-acetylthio-2-methylpropionic acid which comprises reacting DL-3-acetylthio-2-methylpropionic acid with an optically active N-substituted phenylalaninol of the formula (I) to form diastereomeric salts, subjecting the formed diastereomeric salts to a fractional crystallization from a solvent to separate the D-acid salt from the L-acid salt, and then decomposing the D-acid salt with a mineral acid to give D-3-acetylthio-2-methylpropionic acid.
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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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- PROLINE DERIVATIVES AND RELATED COMPOUNDS
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New proline derivatives and related compounds which have the general formula STR1 are useful as angiotensin converting enzyme inhibitors.
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