(5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid sodium salt | 102209-75-6

• 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
• 英文名称: (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid sodium salt
• 英文别名: sodium (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylate；sodium;(5R,6Z)-6-[(1-methyltriazol-4-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
• CAS: 102209-75-6
• 化学式: C₁₀H₇N₄O₃S*Na
• 分子量: 286.246
• InChiKey: OMJBLZMKGVWHQP-VKVLVNHFSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.29
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  116
• 氢给体数：
  0
• 氢受体数：
  6

制备方法与用途

生物活性

BRL-42715 是一种广泛有效的细菌 β-内酰胺酶抑制剂。

靶点

β-内酰胺酶（Beta-lactamase）

反应信息

• 作为反应物：
  描述：

  (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid sodium salt 在 potassium tert-butylate 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 1.17h， 生成 司他夫定
  参考文献：
  名称：

  Synthesis of some 2′,3′-didehydro-2′,3′-dideoxynucleosides derived from modified pyrimidine bases

  摘要：

  3'.5'-Bis-O-(4-tolylsulfonyl)-thymidine and -2'-deoxyuridine (13a and 13b) reacted with sodium ethoxide in boiling ethanol to give the corresponding ethoxy-oxetanes 12a and 12b in 67 and 66% overall yield for the two-step processes starting from thymidine 4a and 2'-deoxyuridine 4b; respectively. Treatment of the ethoxy-oxetanes 12a and 12b with hydrogen sulfide and N-1,N-1,N-3,N-3- tetramethylguanidine in dry pyridine solution gave the 2-thiothymine- and 2-thiouracil-derived oxetanes 19a and 19b in 62 and 68.5% yield, respectively. When the latter compounds were treated with potassium tert-butoxide in dimethyl sulfoxide, the corresponding 2',3'-didehydro-2',3'-dideoxynucleosides (d4 nucleosides) 10a and 10b were obtained in 66 and 60% yield. respectively. The 2-thiothymine-derived oxetane 19a was converted via the 5-methyl-2-thiocytosine-derived oxetane 21a into the 5-methyl-2-thiocytosine-derived d4 nucleoside 11a in 59.5% overall yield; the 2-thiouracil-derived oxetane 19b was similarly converted into the 2-thiocytosine- and 4-N-methyl-2-thiocytosine-derived d4 nucleosides 11b and 23 in 51 and 50% overall yield, respectively. Finally, the ethoxy-oxetane 12b was converted into the corresponding amino- and methylamino-oxetanes 25a and 25b in 74 and 83% yield, respectively. The latter compound. 25b, was successfully converted into the 2-N-methylisocytosine-derived d4 nucleoside 26b in 62% yield.

  DOI：

  10.1039/p19940000189
• 作为产物：
  描述：

  (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid p-nitrobenzyl ester 生成 (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid sodium salt
  参考文献：
  名称：

  BENNETT, I.;BROOM, N. J. P.;BRUTON, G.;CALVERT, S.;CLARKE, B. P.;COLEMAN,+, J. ANTIBIOTICS., 44,(1991) N, C. 331-337

  摘要：

  DOI：

文献信息

• A novel and stereocontrolled synthesis of (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid, a potent broad spectrum β-lactamase inhibitor
  作者：Neal F. Osborne、Nigel J. P. Broom、Steven Coulton、John B. Harbridge、Michael A. Harris、Irene Stirling-François、Graham Walker

  DOI：10.1039/c39890000371

  日期：——

  the condensation of the anion, generated by deprotonation of p-methoxybenzyl (5R,6S)-6-bromopenem-3-carboxylate(10), with 1-methyl-1,2,3-triazole-4-carbaldehyde; in situ acylation, followed by reductive elimination afforded the isomeric (Z)- and (E)-6-triazolylmethylene penem esters, (12) and (13) respectively.

  由6-氨基青霉烯酸制备标题化合物（BRL 42715）的关键步骤是阴离子的缩合反应，该阴离子是由对甲氧基苄基（5 R，6 S）-6-溴openem-3-羧酸酯（10）去质子化而生成的），1-甲基-1,2,3-三唑-4-甲醛; 原位酰化，然后进行还原消除，分别得到异构体（Z）-和（E）-6-三唑基亚甲基戊二烯酸酯，分别为（12）和（13）。
• Studies on the mechanism of action of (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid (BRL 427 15), a potent inhibitor of bacterial β-lactamase
  作者：Nigel J. P. Broom、Tony H. Farmer、Neal F. Osborne、John W. Tyler

  DOI：10.1039/c39920001663

  日期：——

  A novel base catalysed rearrangement of (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid (BRL 427 15) is reported together with its implications concerning the mechanism of inactivation of β-lactamases by this compound.

  报告了(5R)-(Z)-6-(1-甲基-1,2,3-三唑-4-基亚甲基)青霉烯-3-羧酸（BRL 427 15）的一种新型碱催化重排，以及该化合物对δ-内酰胺酶灭活机制的影响。
• Kinetic study of interaction between BRL 42715, beta-lactamases, and D-alanyl-D-alanine peptidases
  作者：A Matagne、P Ledent、D Monnaie、A Felici、M Jamin、X Raquet、M Galleni、D Klein、I François、J M Frère

  DOI：10.1128/aac.39.1.227

  日期：1995.1

  A detailed kinetic study of the interactions between BRL 42715, a beta-lactamase-inhibiting penem, and various beta-lactamases (EC 3.5.2.6) and D-alanyl-D-alanine peptidases (DD-peptidases, EC 3.4.16.4) is presented. The compound was a very efficient inactivator of all active-site serine beta-lactamases but was hydrolyzed by the class B, Zn(2+)-containing enzymes, with very different kcat values. Inactivation of the Streptomyces sp. strain R61 extracellular DD-peptidase was not observed, and the Actinomadura sp. strain R39 DD-peptidase exhibited a low level of sensitivity to the compound.

  本文介绍了BRL 42715与各种β-内酰胺酶(EC 3.5.2.6)和D-丙氨酸-D-丙氨酸肽酶(DD-肽酶，EC 3.4.16.4)之间相互作用的详细动力学研究。该化合物是所有活性位点丝氨酸β-内酰胺酶的高效灭活剂，但被B类、含Zn2+的酶水解，其kcat值非常不同。未观察到对Streptomyces sp.菌株R61胞外DD-肽酶的灭活作用，而Actinomadura sp.菌株R39 DD-肽酶对该化合物的敏感性较低。
• OSBORNE, NEAL F.;BROOM, NIGEL J. P.;COULTON, STEVEN;HARBRIDGE, JOHN B.;HA+, J. CHEM. SOC. CHEM. COMMUN.,(1989) N, C. 371-373
  作者：OSBORNE, NEAL F.、BROOM, NIGEL J. P.、COULTON, STEVEN、HARBRIDGE, JOHN B.、HA+

  DOI：——

  日期：——
• Synthesis of some 2′,3′-didehydro-2′,3′-dideoxynucleosides derived from modified pyrimidine bases
  作者：Colin B. Reese、Chamakura V. N. S. Varaprasad

  DOI：10.1039/p19940000189

  日期：——

  3'.5'-Bis-O-(4-tolylsulfonyl)-thymidine and -2'-deoxyuridine (13a and 13b) reacted with sodium ethoxide in boiling ethanol to give the corresponding ethoxy-oxetanes 12a and 12b in 67 and 66% overall yield for the two-step processes starting from thymidine 4a and 2'-deoxyuridine 4b; respectively. Treatment of the ethoxy-oxetanes 12a and 12b with hydrogen sulfide and N-1,N-1,N-3,N-3- tetramethylguanidine in dry pyridine solution gave the 2-thiothymine- and 2-thiouracil-derived oxetanes 19a and 19b in 62 and 68.5% yield, respectively. When the latter compounds were treated with potassium tert-butoxide in dimethyl sulfoxide, the corresponding 2',3'-didehydro-2',3'-dideoxynucleosides (d4 nucleosides) 10a and 10b were obtained in 66 and 60% yield. respectively. The 2-thiothymine-derived oxetane 19a was converted via the 5-methyl-2-thiocytosine-derived oxetane 21a into the 5-methyl-2-thiocytosine-derived d4 nucleoside 11a in 59.5% overall yield; the 2-thiouracil-derived oxetane 19b was similarly converted into the 2-thiocytosine- and 4-N-methyl-2-thiocytosine-derived d4 nucleosides 11b and 23 in 51 and 50% overall yield, respectively. Finally, the ethoxy-oxetane 12b was converted into the corresponding amino- and methylamino-oxetanes 25a and 25b in 74 and 83% yield, respectively. The latter compound. 25b, was successfully converted into the 2-N-methylisocytosine-derived d4 nucleoside 26b in 62% yield.