(3S,4R)-3-氨基-4-甲基氧-2-酮 | 131131-06-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (3S,4R)-3-氨基-4-甲基氧-2-酮
• 英文名称: (3S,4R)-3-amino-4-methyl-2-oxetanone p-toluenesulfonate salt
• 英文别名: L-Threonine β-lactone tosylate；(3S,4R)-2-methyl-4-oxo-3-oxetanylammonium toluene-4-sulfonate；(2S,3R)-β-lactone；4-methylbenzenesulfonate;[(2R,3S)-2-methyl-4-oxooxetan-3-yl]azanium
• CAS: 131131-06-1
• 化学式: C₄H₇NO₂*C₇H₈O₃S
• 分子量: 273.31
• InChiKey: LIPLHVDXIYGFLG-RCROYASPSA-N

物化性质

• 熔点：
  120 °C (decomp)(Solv: ethyl ether (60-29-7))

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,4R)-3-氨基-4-甲基氧-2-酮 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 0.25h， 以92%的产率得到hydrobromide salt of (2R,3S)-2-amino-3-bromobutanoic acid
  参考文献：
  名称：

  Synthesis and acylation of salts of L-threonine .beta.-lactone: a route to .beta.-lactone antibiotics

  摘要：

  The synthesis and N-acylation of beta-lactones derived from L-threonine and L-allo-threonine were investigated. Treatment of N-[(o-nitrophenyl)sulfenyl]-L-threonine (7a) and N-[(o-nitrophenyl)sulfenyl]-L-allo-threonine (7b) with 4-bromobenzenesulfonyl chloride in pyridine at -43 to -0-degrees-C gives the corresponding-beta-lactones 8a and 8b, respectively, in 45-56% yields. These can be deprotected with thiophenol or p-thiocresol in the presence of p-toluenesulfonic acid to produce optically pure salts of L-threonine-beta-lactone (9a) and its allo isomer 9b (65-92%). Compound 9a is readily acylated by reagents such as acid chlorides (e.g., acetyl, benzoyl) and mixed anhydrides to afford N-acyl-beta-substituted-beta-lactones such as 10 (antibiotic SQ 26,517), 14, 15, and 16 in good yield (84-92%). Reaction of beta-lactones 8a, 8b, and 9a with HBr in acetic acid results in nucleophilic ring opening by bromide at the beta-position to give pure isomers of 2-amino-3-bromobutanoic acid.

  DOI：

  10.1021/jo00003a062
• 作为产物：
  描述：

  对甲苯磺酸 、 (3S,4R)-3-(t-butoxycarbonylamino)-4-methyloxetan-2-one 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以85%的产率得到(3S,4R)-3-氨基-4-甲基氧-2-酮
  参考文献：
  名称：

  LACTONE-BASED PROBES AND METHODS OF USE THEREOF

  摘要：

  该发明提供了一个式I的化合物： 或其盐，其中R 1 ，R 2 ，R 3 ，R 4 ，L 1 ，L 2 和Y具有规范中描述的任何值，以及包含式I的化合物的组合物。这些化合物可用于标记青霉素结合蛋白（PBPs）。

  公开号：

  US20180339972A1

文献信息

• Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
  申请人：The Regents of the University of California

  公开号：US09353075B2

  公开（公告）日：2016-05-31

  The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

  本发明提供了用于抑制N-酰基乙醇胺酸酰胺酶（NAAA）的化合物和药物组合物。考虑到抑制NAAA是一种维持棕榈酰乙醇胺（PEA）和油酰乙醇胺（OEA）水平的方法，在特征为PEA和OEA浓度降低的情况下。该发明还提供了治疗炎症性疾病和疼痛以及其他与降低PEA和OEA水平相关的紊乱的方法。
• Synthesis and Structure−Activity Relationships of <i>N</i>-(2-Oxo-3-oxetanyl)amides as <i>N</i>-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors
  作者：Carlos Solorzano、Francesca Antonietti、Andrea Duranti、Andrea Tontini、Silvia Rivara、Alessio Lodola、Federica Vacondio、Giorgio Tarzia、Daniele Piomelli、Marco Mor

  DOI：10.1021/jm100582w

  日期：2010.8.12

  The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist of peroxisome proliferator-activated receptor-alpha, palmitoylethanolamide (PEA). FAEs are hydrolyzed intracellularly by either fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase (NAAA). Selective inhibition of NAAA by (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from the structure of 7a, a series of beta-lactones was prepared and tested on recombinant rat NAAA to explore structure-activity relationships (SARs) for this class of inhibitors and improve their in vitro potency. Following the hypothesis that these compounds inhibit NAAA by acylation of the catalytic cysteine, we identified several requirements for recognition at the active site and obtained new potent inhibitors. In particular, (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide (7h) was more potent than 7a at inhibiting recombinant rat NAAA activity (7a, IC(50) = 420 nM; 7h, IC(50) = 115 nM) in vitro and at reducing carrageenan-induced leukocyte infiltration in vivo.
• Synthesis, Stability, and Antimicrobial Activity of (+)-Obafluorin and Related .beta.-Lactone Antibiotics
  作者：Yunlong Pu、Christopher Lowe、Miloslav Sailer、John C. Vederas

  DOI：10.1021/jo00092a025

  日期：1994.7

  Optically pure obafluorin(l), an antibacterial agent from Pseudomonas fluorescens, was synthesized in six steps via lactonization of N-[(2-nitrophenyl)sulfenyl]-(2S,3R)-2-amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid (12a), which was prepared in a stereospecific manner from 4-nitrophenylacetaldehyde (9a) and (S)-1-benzoyl-2-tert-butyl-3-methyl-4-imidazolidinone (7). A series of analogues was then synthesized in order to probe structural features required for antibacterial activity as well as those responsible for the hydrolytic decomposition of 1 to the corresponding hydroxy acid 23a. Analogues 22b and 22e wherein the nitro group of 1 is replaced with hydrogen and chlorine, respectively, were prepared in a fashion similar to 1, as were the N-acetyl, N-benzoyl, and N-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetyl (ATMO) derivatives 24a-c. The tosylate salt of L-threonine-beta-lactone (21) was transformed to a series of N-acylated derivatives including the following: 22d (2,3-dihydroxybenzoyl), 25 (2-hydroxybenzoyl), 27 (3,4-dihydroxybenzoyl), 29 (4'methyl-2,2'-bipyridine-4-carbonyl), 31 (epsilon-(L-alpha-aminoadipoyl)), 34 ((N'-2,3-dihydroxybenzoyl)-beta-alanyl), 35 (bromoacetyl), 36 ((6-purinylthio)acetyl), and 37 ((4-pyridylthio)acetyl). The results show that a-amino beta-lactones bearing an N-acyl group with an o- or p-hydroxybenzoyl moiety are especially prone to decomposition under aqueous conditions and that this effect is enhanced by replacement of the 4-nitrobenzyl group on the oxetanone ring of 1 with a methyl. The N-(3,4-dihydroxybenzoyl)L-threonine beta-lactone (27) converts slowly in the solid state to (4S,5S)-2-(3,4-dihydroxybenzoyl)-5-methyl-2-oxazoline-4-carboxylic acid (39b), which hydrolyzes rapidly in 4:1 CD3CN:D2O to O-(3,4-dihydroxybenzoyl)-L-allothreonine (38b). Direct hydrolysis of 27 to 38b under the same conditions has a half-life of 2.4 days. Preliminary assays for antibacterial activity indicate that 29 has nearly comparable activity to obafluorin(l) but is much more stable. The (2-nitrophenyl)sulfenyl p-lactones 14 and 41, as well as the N-(phenylsulfenyl)-L-threonine beta-lactone (44), are the most active agents in the biological assays.
• PU, YUNLONG;MARTIN, FIONNA M.;VEDERAS, JOHN C., J. ORG. CHEM., 56,(1991) N, C. 1280-1283
  作者：PU, YUNLONG、MARTIN, FIONNA M.、VEDERAS, JOHN C.

  DOI：——

  日期：——
• LACTONE-BASED PROBES AND METHODS OF USE THEREOF
  申请人：REGENTS OF THE UNIVERSITY OF MINNESOTA

  公开号：US20180339972A1

  公开（公告）日：2018-11-29

  The invention provides a compound of formula I: or a salt thereof, wherein R 1 , R 2 , R 3 , R 4 , L 1 , L 2 and Y have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful for labeling penicillin-binding proteins (PBPs).

  该发明提供了一个式I的化合物： 或其盐，其中R 1 ，R 2 ，R 3 ，R 4 ，L 1 ，L 2 和Y具有规范中描述的任何值，以及包含式I的化合物的组合物。这些化合物可用于标记青霉素结合蛋白（PBPs）。