p-methoxybenzyl glyoxylate monohydrate | 92771-89-6

• 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: p-methoxybenzyl glyoxylate monohydrate
• 英文别名: 4-Methoxybenzyl dihydroxyacetate；(4-methoxyphenyl)methyl 2,2-dihydroxyacetate
• CAS: 92771-89-6
• 化学式: C₁₀H₁₂O₅
• 分子量: 212.202
• InChiKey: ARTDIKXZWCSNPO-UHFFFAOYSA-N

物化性质

• 沸点：
  350.5±32.0 °C(Predicted)
• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  p-methoxybenzyl glyoxylate monohydrate 在 2,6-二甲基吡啶 、 氯化亚砜 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 20.27h， 生成 (R)-6-(1-Acetoxy-ethyl)-6-bromo-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-methoxy-benzyl ester
  参考文献：
  名称：

  Synthesis of 6-(substituted methylene) carbapenem derivatives from 6-aminopenicillanic acid

  摘要：

  The key intermediate in the preparation of novel 6-(substituted methylene) carbapenem derivatives is p-methoxybenzyl (5R,6R)-6-bromo-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate 26, which was prepared in several steps from 6-aminopenicillanic acid 14 via (3R,4R)-4-allyl-3-bromoazetidin-2-one 21. Sequential treatment of the aforementioned ester 26 with either lithium diisopropylamide or lithium diphenylamide, 1-methyl-1H-1,2,3-triazole-4-carbaldehyde and acetic anhydride provided a diastereoisomeric mixture of acylated bromohydrins 28; reductive elimination then afforded the isomeric (E)- and (Z)-6-triazolylmethylene carbapenem esters 29 and 31, respectively. Lewis acid-mediated deprotection of the 6-bromo and 6-[(E)-triazolylmethylene] esters 26 and 29 gave the sodium salts of (5R,6R)-6-bromo-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 27 and (5R)-6-[(E)-(1-methyl-1H-1,2,3-triazol-4-yl)methylene]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 30, respectively.In addition, condensation of the anion, generated by deprotonation of the 6-bromo ester, with acetaldehyde, followed by acylation and reductive elimination furnished the isomeric (E)- and (Z)-ethylidene carbapenem esters.Whilst the (E)-6-triazolylmethylene carbapenem displayed low levels of antibacterial activity, it possessed no beta-lactamase-inhibitory activity whatsoever. The 6-bromocarbapenem was devoid of both antibacterial and beta-lactamase-inhibitory activity.

  DOI：

  10.1039/p19910002699
• 作为产物：
  描述：

  bis-(p-methoxybenzyl) tartrate 在 lead(IV) acetate 作用下， 以 苯 为溶剂， 反应 1.5h， 以95%的产率得到p-methoxybenzyl glyoxylate monohydrate
  参考文献：
  名称：

  Synthesis of 6-(substituted methylene) carbapenem derivatives from 6-aminopenicillanic acid

  摘要：

  The key intermediate in the preparation of novel 6-(substituted methylene) carbapenem derivatives is p-methoxybenzyl (5R,6R)-6-bromo-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate 26, which was prepared in several steps from 6-aminopenicillanic acid 14 via (3R,4R)-4-allyl-3-bromoazetidin-2-one 21. Sequential treatment of the aforementioned ester 26 with either lithium diisopropylamide or lithium diphenylamide, 1-methyl-1H-1,2,3-triazole-4-carbaldehyde and acetic anhydride provided a diastereoisomeric mixture of acylated bromohydrins 28; reductive elimination then afforded the isomeric (E)- and (Z)-6-triazolylmethylene carbapenem esters 29 and 31, respectively. Lewis acid-mediated deprotection of the 6-bromo and 6-[(E)-triazolylmethylene] esters 26 and 29 gave the sodium salts of (5R,6R)-6-bromo-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 27 and (5R)-6-[(E)-(1-methyl-1H-1,2,3-triazol-4-yl)methylene]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 30, respectively.In addition, condensation of the anion, generated by deprotonation of the 6-bromo ester, with acetaldehyde, followed by acylation and reductive elimination furnished the isomeric (E)- and (Z)-ethylidene carbapenem esters.Whilst the (E)-6-triazolylmethylene carbapenem displayed low levels of antibacterial activity, it possessed no beta-lactamase-inhibitory activity whatsoever. The 6-bromocarbapenem was devoid of both antibacterial and beta-lactamase-inhibitory activity.

  DOI：

  10.1039/p19910002699

文献信息

• Carbapenem and penem antibiotics. III. Synthesis and antibacterial activity of 2-functionalized-methyl penems related to asparenomycins.
  作者：MITSURU IMUTA、SHOICHIRO UYEO、MASAO NAKANO、TADASHI YOSHIDA

  DOI：10.1248/cpb.33.4371

  日期：——

  Racemic and optically active 2-(heteroaromatic) thiomethyl penems having a 1-(hydroxymethyl) ethylidene or cyclic carbonate side-chain at C-6 (24, 51, 63, 65, 37, 40, 69 and 21b, 61b, 26b, 30b, 64b, 35b, 66b, 39b, 68b) were synthesized, and their antibacterial activities are determined.

  合成了具有C-6位1-(羟甲基)亚乙基或环状碳酸酯侧链的R构型和光学活性2-(杂芳基)硫代甲基青霉烯（24、51、63、65、37、40、69以及21b、61b、26b、30b、64b、35b、66b、39b、68b），并测定了它们的抗菌活性。
• Carbapenem and penem antibiotics. II. Synthesis and antibacterial activity of 2-functionalized-methyl carbapenems related to asparenomycins.
  作者：MITSURU IMUTA、HISAO ONA、SHOICHIRO UYEO、KIYOSHI MOTOKAWA、TADASHI YOSHIDA

  DOI：10.1248/cpb.33.4361

  日期：——

  Racemic 2-acetoxymethyl and 2-(heteroaromatic) thiomethyl carbapenems having a 1-(hydroxymethyl) ethylidene or cyclic carbonate side-chain at C-6 (5, 25, 38, 40, 42, and 36b, 23b, 28b, 30b, 32b, 34b) were synthesized from the common intermediates 3a and 3b, and their antibacterial activities were determined.

  具有C-6位的1-(羟甲基)亚乙基或环状碳酸酯侧链的Racemic 2-乙酰氧甲基和2-(杂芳基)硫甲基碳青霉烯化合物（5、25、38、40、42和36b、23b、28b、30b、32b、34b）通过共同中间体3a和3b合成，并测定了它们的抗菌活性。
• Carbapenem and penem antibiotics. IV. Synthesis and antibacterial activity of (5R*,6S*)-6-((R*)-1-hydroxyethyl)-2-functionalized-methyl carbapenem and penem derivatives.
  作者：HISAO ONA、SHOICHIRO UYEO、TAKASHI FUKAO、MASAYOSHI DOI、TADASHI YOSHIDA

  DOI：10.1248/cpb.33.4382

  日期：——

  Racemic 2-acetoxymethyl and 2-(heteroaromatic) thiomethyl carbapenem and penem antibiotics having a 1-(R*)-hydroxyethyl side-chain at C-6 (6, 7, 8, and 45, 59, 47, 49, 51) were synthesized, and their antibacterial activities were determined.

  合成了R enantiomer的2-乙酰氧基甲基和2-(杂环芳香)硫甲基的碳青霉烯和青霉素抗生素，这些化合物在C-6位上具有1-(R*)-羟基乙基侧链（6, 7, 8，以及45, 59, 47, 49, 51），并测定了它们的抗菌活性。
• 9-oxo-1-azabicyclo\x9b5.2.0!non-2,4-diene-2-carboxylic acid compounds as
  申请人：Zeneca Limited

  公开号：US05719139A1

  公开（公告）日：1998-02-17

  The present invention provides a compound of the formula (I): ##STR1## wherein R.sup.1 is hydrogen, optionally substituted; acylamino, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, C.sub.1-6 alkanoyloxy, C.sub.1-6 alkylamino, di-(C.sub.1-6 alkyl)amino, C.sub.1-6 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl or di-(C.sub.1-6 alkyl)aminocarbonyl; R.sup.2 is hydrogen or C.sub.1-6 alkoxy; or R.sup.1 and R.sup.2 together form optionally substituted C.sub.1-6 alkylene; R.sup.3 and R.sup.5 are independently hydrogen or C.sub.1-6 alkyl; and one of R.sup.4 and R.sup.6 is hydrogen or C.sub.1-4 alkyl and the other is selected from a number of groups or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. Processes of their preparation, intermediates in their preparation, their use as therapeutic agents and pharmaceutical compositions containing them.

  本发明提供了化合物的公式(I)：##STR1##其中R.sup.1是氢，可选地取代的；酰胺基，C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.1-6烷氧基，C.sub.1-6烷酰氧基，C.sub.1-6烷基氨基，二-(C.sub.1-6烷基)氨基，C.sub.1-6烷氧羰基，氨基羰基，C.sub.1-6烷基氨基羰基或二-(C.sub.1-6烷基)氨基羰基；R.sup.2是氢或C.sub.1-6烷氧基；或R.sup.1和R.sup.2一起形成可选取代的C.sub.1-6烷基；R.sup.3和R.sup.5独立地是氢或C.sub.1-6烷基；R.sup.4和R.sup.6中的一个是氢或C.sub.1-4烷基，另一个被选择自多个基团或其药学上可接受的盐或体内水解酯。它们的制备方法，制备中间体，作为治疗剂的用途以及含有它们的药物组合物。
• Novel C-2 Substituted Carbapenem Derivatives Part III. Synthesis and Biological Activity of 2-(Functionalised Ethenyl, Oxyiminomethyl and .ALPHA.-(Hydroxy)benzyl)-Carbapenems.
  作者：NICOLA J. C. CLEAR、JOHN S. DA VIES、A. JOHN EGLINGTON、STEPHEN C. M. FELL、JEREMY D. HINKS、NICHOLAS W. HIRD、ERIC HUNT、STEPHEN F. MOSS、MICHAEL J. PEARSON

  DOI：10.7164/antibiotics.50.237

  日期：——

  The synthesis, antibacterial activity and stability to human dehydropeptidase-1 (DHP-1) of three small series of carbapenems carrying carbon-linked substituents at C-2 are described. C-2 Ethenyl carbapenems showed moderate antibacterial activity but poor stability to DHP-1. C-2 Oxyiminomethyl carbapenems demonstrated variable activity and stability. C-2 α-(Hydroxy)benzyl carbapenems were the most promising and showed good potency and DHP-1 stability.

  描述了三系列在C-2位带有碳链取代基的碳青霉烯类化合物的合成、抗菌活性及其对人类脱氢肽酶-1（DHP-1）的稳定性。C-2位的乙烯基碳青霉烯显示出中等的抗菌活性，但对DHP-1的稳定性较差。C-2位的羟亚胺甲基碳青霉烯表现出可变的活性和稳定性。C-2位的α-(羟基)苯甲基碳青霉烯是最有前途的，显示出良好的效力和对DHP-1的稳定性。