threo-(1R,2R)-1-(4-nitrophenyl)-2-(dichloroacetamido)-1,3-propanediol 3-butanoate | 59005-99-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: threo-(1R,2R)-1-(4-nitrophenyl)-2-(dichloroacetamido)-1,3-propanediol 3-butanoate
• 英文别名: 3-butanoylchloramphenicol；Butanoic acid, 2-[(dichloroacetyl)amino]-3-hydroxy-3-(4-nitrophenyl)propyl ester, [R-(R*,R*)]-；[(2R,3R)-2-[(2,2-dichloroacetyl)amino]-3-hydroxy-3-(4-nitrophenyl)propyl] butanoate
• CAS: 59005-99-1
• 化学式: C₁₅H₁₈Cl₂N₂O₆
• 分子量: 393.224
• InChiKey: OCBSZMQTKMKOSN-DGCLKSJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  threo-(1R,2R)-1-(4-nitrophenyl)-2-(dichloroacetamido)-1,3-propanediol 3-butanoate 、 丙酰氯 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以95%的产率得到1-propanoyl-3-butanoylchloramphenicol
  参考文献：
  名称：

  Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics

  摘要：

  A functional metagenomic approach identified novel and diverse soil-derived DNAs encoding inhibitors to methicillin-resistant Staphylococcus aureus (MRSA). A metagenomic DNA soil library containing 19 200 recombinant Escherichia coli BAC clones with 100 Kb average insert size was screened for antibiotic activity. Twenty-seven clones inhibited MRSA, seven of which were found by LC-MS to possess modified chloramphenicol (Cm) derivatives, including three new compounds whose structures were established as 1-acetyl-3-propanoylchloramphenicol, 1-acety1-3-butanoyl-chloramphenicol, and 3-butanoyl-1-propanoylchloramphenicol. Cm was used as the selectable antibiotic for cloning, suggesting that heterologously expressed enzymes resulted in derivatization of Cm into new chemical entities with biological activity. An esterase was found to be responsible for the enzymatic regeneration of Cm, and the gene trfA responsible for plasmid copy induction was found to be responsible for inducing antibacterial activity in some clones. Six additional acylchloramphenicols were synthesized for structure and antibacterial activity relationship studies, with 1-p-nitrobenzoylchloramphenicol the most active against Mycobacterium intracellulare and Mycobacterium tuberculosis, with MICs of 12.5 and 50.0 mu g/mL, respectively.

  DOI：

  10.1021/acs.jnatprod.7b00903
• 作为产物：
  描述：

  正丁酸乙烯酯 、 氯霉素 在 lipase cloned from Bacillus amyloliquefaciens 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 threo-(1R,2R)-1-(4-nitrophenyl)-2-(dichloroacetamido)-1,3-propanediol 3-butanoate
  参考文献：
  名称：

  解淀粉芽孢杆菌脂肪酶酯交换合成氯霉素酯

  摘要：

  这项工作提出了一种利用脂肪酶的高对映选择性和区域选择性来生产氯霉素酯的合成路线。使用氯霉素、不同碳链长度的酰基供体和脂肪酶LipBA（从解淀粉芽孢杆菌克隆的脂肪酶）合成了一系列氯霉素酯。在具有不同碳链长度的酰基供体中，发现丙酸乙烯酯是最好的。研究了不同有机溶剂、反应温度、反应时间、酶载量和含水量对氯霉素酯合成的影响。使用 4.0 g L-1 LipBA 负载合成氯霉素丙酸酯 (0.25 M)，在 1,4-二恶烷作为溶剂中，50 °C 下，8 小时内转化率约为 98%，纯度约为 99%。丙酸乙烯酯与氯霉素的最佳摩尔比提高到5:1。这是首次报道解淀粉芽孢杆菌脂肪酶用于氯霉素酯合成，并详细研究了使用该反应合成丙酸氯霉素。高酶活性和选择性使脂肪酶 LipBA 成为具有复杂结构的分子的绿色化学合成的有吸引力的催化剂。

  DOI：

  10.3390/molecules22091523

文献信息

• [EN] USE OF alpha-PHENYLTHIOCARBOXYLIC AND alpha-PHENYLOXYCARBOXYLIC ACIDS WITH SERUM-GLUCOSE-LOWERING AND SERUM-LIPID-LOWERING ACTIVITY<br/>[FR] UTILISATION D'ACIDES 20040708WO03059875A2SIGMA TAU IND FARMACEUTI [IT], et al200307241,74-7,14,17,18,20-26PX1-7,10,15PXWINEGAR D A ET AL: "Role of peroxisome proliferator-activated receptors in atherosclerosis", CURRENT OPINION IN CARDIOVASCULAR, PULMONARY AND RENAL INVESTIGATIONAL DRUGS 2000 UNITED KINGDOM, vol. 2, no. 3, 2000, pages 233 - 243, XP008029337, ISSN: 1464-8482WINEGAR D A ET ALRole of peroxisome proliferator-activated receptors in atherosclerosisCURRENT OPINION IN CARDIOVASCULAR, PULMONARY AND RENAL INVESTIGATIONAL DRUGS 2000 UNITED KINGDOM2000231464-8482233243page 236, left-hand column, last paragraph237L1,2<table>1</table>X1,2,7,8,10-12,15XBROOKS D A ET AL: "Design and synthesis of 2-methyl-2-{4-[2-(5-methyl-2- aryloxazol-4-yl)ethoxy]phenoxy}propionic acids: a new class of dual PPARalpha/gamma agonists", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 44, no. 13, 21 June 2001 (2001-06-21), pages 2061 - 2064, XP002184099, ISSN: 0022-2623BROOKS D A ET ALDesign and synthesis of 2-methyl-2-{4-[2-(5-methyl-2- aryloxazol-4-yl)ethoxy]phenoxy}propionic acids: a new class of dual PPARalpha/gamma agonistsJOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US2001062144130022-262320612064Chart 1<table>1</table>2063R1,2X1-3,7,10-12,15XLALEZARI I ET AL: "LR-16 A COMPOUND WITH POTENT EFFECTS ON THE OXYGEN AFFINITY OF HEMOGLOBIN ON BLOOD CHOLESTEROL AND ON LOW DENSITY LIPOPROTEIN", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 85, no. 16, 1988, 1988, pages 6117 - 6121, XP001161155, ISSN: 0027-8424LALEZARI I ET ALLR-16 A COMPOUND WITH POTENT EFFECTS ON THE OXYGEN AFFINITY OF HEMOGLOBIN ON BLOOD CHOLESTEROL AND ON LOW DENSITY LIPOPROTEINPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES1988198885160027-842461176121Scheme 1page 6117, abstractX1,2,10-12,15XUS3262850AMOSS JONES WILLIAM GLYNNE, et al19660726111719X1,2,10-12,15XGB1422679AFUNAI PHARMACEUTICAL IND LTD19760128112126X1,2,7,10-12,15XGRONOWITZ S ET AL: "POTENTIAL HYPOLIPIDEMIC AGENTS XIX. SYNTHESIS AND LIPID-LOWERING PROPERTIES OF THIOPHENE DERIVATIVES RELATED TO CLOFIBRATE", ACTA PHARMACEUTICA SUECICA, XX, XX, vol. 15, no. 5, 1978, pages 361 - 367, XP001053343, ISSN: 0001-6675GRONOWITZ S ET ALPOTENTIAL HYPOLIPIDEMIC AGENTS XIX. SYNTHESIS AND LIPID-LOWERING PROPERTIES OF THIOPHENE DERIVATIVES RELATED TO CLOFIBRATEACTA PHARMACEUTICA SUECICA, XX, XX19781550001-6675361367<table>1</table>3641X1,3,10-12,15XDURIEZ P ET AL: "POST-STATIN APPROACHES TO HYPERLIPIDAEMIA", EXPERT OPINION ON INVESTIGATIONAL DRUGS, ASHLEY PUBLICATIONS LTD., LONDON, GB, vol. 7, no. 12, December 1998 (1998-12-01), pages 1997 - 2009, XP000892408, ISSN: 1354-3784DURIEZ P ET ALPOST-STATIN APPROACHES TO HYPERLIPIDAEMIAEXPERT OPINION ON INVESTIGATIONAL DRUGS, ASHLEY PUBLICATIONS LTD., LONDON, GB1998127121354-37841997200920023.1Y1-15YBROWN P J ET AL: "A Ureido-Thiobutyric Acid (GW9578) is a subtype-Selective PPARalpha Agonist with Potent lipid-Lowering Activity", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 42, no. 19, 9 April 1999 (1999-04-09), pages 3785 - 3788, XP002128791, ISSN: 0022-2623BROWN P J ET ALA Ureido-Thiobutyric Acid (GW9578) is a subtype-Selective PPARalpha Agonist with Potent lipid-Lowering ActivityJOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US1999040942190022-262337853788Chart 1page 3787, left-hand column, last paragraphY1-15YGUERRE-MILLO MICHELE ET AL: "Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 275, no. 22, 2 June 2000 (2000-06-02), pages 16638 - 16642, XP002275720, ISSN: 0021-9258GUERRE-MILLO MICHELE ET ALPeroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposityJOURNAL OF BIOLOGICAL CHEMISTRY20000602275220021-9258166381664216641R3Y1-15YZHANG BEI B ET AL: "New approaches in the treatment of type 2 diabetes", CURRENT OPINION IN CHEMICAL BIOLOGY, vol. 4, no. 4, August 2000 (2000-08-01), pages 461 - 467, XP002275721, ISSN: 1367-5931ZHANG BEI B ET ALNew approaches in the treatment of type 2 diabetesCURRENT OPINION IN CHEMICAL BIOLOGY200008441367-5931461467463L31Y1-15YHAWKE ROY L ET AL: "Potent hypocholesterolemic activity of novel ureido phenoxyisobutyrates correlates with their intrinsic fibrate potency and not with their ACAT inhibitory activity", JOURNAL OF LIPID RESEARCH, vol. 38, no. 6, 1997, pages 1189 - 1203, XP002275722, ISSN: 0022-2275HAWKE ROY L ET ALPotent hypocholesterolemic activity of novel ureido phenoxyisobutyrates correlates with their intrinsic fibrate potency and not with their ACAT inhibitory activityJOURNAL OF LIPID RESEARCH19973860022-227511891203entire documentAA
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2004056355A1

  公开（公告）日：2004-07-08

  The use is described of derivatives of α-phenylthiocarboxylic and α-phenyloxycarboxylic acids with formula (I): in which the substituents have the meanings described in the text, for the preparation of a medicine for the prophylaxis and treatment of diabetes, particularly type 2 diabetes, its complications, the various forms of insulin resistance, and hyperlipidaemias.

  本文描述了使用具有以下公式（I）的α-苯基硫代羧酸和α-苯基氧羧酸的衍生物进行制备药物，用于预防和治疗糖尿病，特别是2型糖尿病、其并发症、各种形式的胰岛素抵抗和高脂血症。其中，取代基的含义在文本中有描述。
• Use of alpha-phenylthiocarboxylic and alpha-phenyloxycarboxylic acids with serum-glucose-lowering and serum-lipid-lowering activity
  申请人：Giannessi Fabio

  公开号：US20060154979A1

  公开（公告）日：2006-07-13

  The use is described of derivatives of α-phenylthiocarboxylic and α-phenyloxycarboxylic acids with formula (i): in which the substituents have the meanings described in the text, for the preparation of a medicine for the prophylaxis and treatment of diabetes, particularly type 2 diabetes, its complications, the various forms of insulin resistance, and hyperlipidaemias.

  使用α-苯基硫代羧酸和α-苯氧羧酸的衍生物(i)来制备一种药物，用于预防和治疗糖尿病，尤其是2型糖尿病，其并发症，各种形式的胰岛素抵抗和高脂血症。其中，取代基的含义如文本所述。
• Reporter gene system for use in cell-based assessment of inhibitors of the hepatitis C virus protease
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US20030082518A1

  公开（公告）日：2003-05-01

  A cell-based assay system in which the detection of the reporter gene activity, or secreted alkaline phosphatase (SEAP), is dependent upon the protease activity of the Hepatitis C virus NS3 gene product. This system can be used to assess the activity of candidate protease inhibitors in a mammalian cell-based assay system. The assay system is simpler than previously described assays due to the use of SEAP which allows the reporter gene activity to be quantified by measuring the amount of secreted gene product in the cell media by monitoring the conversion of luminescent or calorimetric alkaline phosphatase substrate.

  一种细胞检测系统，其中报告基因活性或分泌型碱性磷酸酶（SEAP）的检测取决于丙型肝炎病毒 NS3 基因产物的蛋白酶活性。该系统可用于在基于哺乳动物细胞的检测系统中评估候选蛋白酶抑制剂的活性。由于使用 SEAP，报告基因的活性可以通过监测发光或热量测定碱性磷酸酶底物的转化，测量细胞介质中分泌基因产物的量来量化，因此该检测系统比以前描述的检测系统更简单。
• Anti-angiogenic proteins and fragments and methods of use thereof
  申请人：Beth Israel Deaconess Medical Center, Inc.

  公开号：US20030144481A1

  公开（公告）日：2003-07-31

  Proteins with anti-angiogenic properties are disclosed, and fragments thereof, and methods of using those proteins and fragments to inhibit or promote angiogenesis.

  本研究公开了具有抗血管生成特性的蛋白质及其片段，以及使用这些蛋白质和片段抑制或促进血管生成的方法。
• Use of 3'-utr's from cysteine proteinase genes cpb2 and cpb2.8 of leishmania for directing stage-specific expression
  申请人：——

  公开号：US20040234551A1

  公开（公告）日：2004-11-25

  The present invention relates to the identification and use of sequence elements present in the intergenic region of Cysteine Proteinase Genes, cpb, in L. mexicana and the observation that the identified sequences are involved in the control of stage-regulated gene expression. Principal uses include the preparation of vaccines.

  本发明涉及半胱氨酸蛋白酶基因 cpb 基因间区序列元件的鉴定和使用。 L. mexicana 并观察到所鉴定的序列参与控制阶段调节基因的表达。主要用途包括制备疫苗。