(6R)-3-formyl-8-oxo-7t-(2-phenyl-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester | 35246-65-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (6R)-3-formyl-8-oxo-7t-(2-phenyl-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
• 英文别名: (6R,7R)-7-benzylcarbonylamino-3-formyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0.]oct-2-ene-2-carboxylic acid benzhydryl ester；Diphenylmethyl 3-formyl-7beta-phenylacetamidoceph-3-em-4-carboxylate；benzhydryl (6R,7R)-3-formyl-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 35246-65-2
• 化学式: C₂₉H₂₄N₂O₅S
• 分子量: 512.586
• InChiKey: LXQDBZIVMSEYBR-UFHPHHKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (6R)-3-formyl-8-oxo-7t-(2-phenyl-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 在 Wilkinson's catalyst 、 苯甲醚 、 三氟乙酸 作用下， 以 苯 为溶剂， 反应 2.0h， 生成 头孢唑肟杂质20
  参考文献：
  名称：

  Neue ?-Lactam-Antibiotika. �ber die Darstellung und Decarbonylierung von 3-Formylcephem-Verbindungen. Modifikationen von Antibiotica, 12. Mitteilung [1]

  摘要：

  AbstractBenzhydrylic esters of 3‐unsubstituted cephem‐4‐carboxylic acids of types 9 and 10 (Scheme 2) are prepared by decarbonylation of esters of 3‐formylcephem compounds of type 2 with tris‐triphenylphosphine‐rhodium chloride. The preparation of the starting materials 2 and 5, as well as of the nucleus 13 is described.

  DOI：

  10.1002/hlca.19740570715
• 作为产物：
  描述：

  diphenylmethyl 7β-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate 在 2-碘酰基苯甲酸 作用下， 以 二甲基亚砜 为溶剂， 反应 8.0h， 以91%的产率得到(6R)-3-formyl-8-oxo-7t-(2-phenyl-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
  参考文献：
  名称：

  Oxidation of Alcohols with o-Iodoxybenzoic Acid in DMSO: A New Insight into an Old Hypervalent Iodine Reagent

  摘要：

  The ultracentennial 10-I-4 iodinane oxide IBX (3; o-iodoxybenzoic acid; 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide) represents a new oxidizing-reagent that successfully joins to the large family of known oxidants. IBX, in contrast to other valuable oxidants, is inexpensive to prepare and easy to handle, can tolerate moisture and water, and generally gives very good yields. Furthermore, IBX is mild and chemoselective (primary alcohols are converted into aldehydes with no overoxidation to acids; 1,2-diols are converted to alpha-ketols or alpha-diketones without oxidative cleavage; amino alcohols are oxidized to amino carbonyls, without protection of the amino group; sensitive heterocycles are not affected; various other functional groups are compatible with IBX oxidation). IBX is versatile (it works in various solvents and it is highly sensitive to temperature variations), and its solutions in DMSO are stable enough to carry out the oxidation reaction easily.

  DOI：

  10.1021/jo00127a036

文献信息

• Cephalosporin derivatives
  申请人：Beecham Group p.l.c.

  公开号：US05064649A1

  公开（公告）日：1991-11-12

  .beta.-Lactam antibiotics of the formula (Ia) or a pharmaceutically acceptable salt or pharmaceutically acceptable in vivo hydrolysable ester thereof are disclosed: ##STR1## wherein R.sup.1 is hydrogen, methoxy or formamido; R.sup.2 is a acyl group, in particular that of an antibacterially active cephalosporin; CO.sub.2 R.sup.6 is carboxy group or a carboxylate anion; R.sup.4 is a butenolide or butanolide ring, optionally substituted by one or two alkyl, dialkylamino, alkoxy, hydroxy or aryl groups, which may be the same or different, or, wherein two adjacent carbon atoms which are available for substitution define the common bond of an aromatic fused bicyclic system; X is S, SO, SO.sub.2, O or CH.sub.2 ; and the dashed line adjacent to R.sup.4 represents an optional double bond. Processes for the preparation of compounds together with intermediates for use therein are disclosed.

  公开了式(Ia)的.beta.-内酰胺类抗生素或其药学上可接受的盐或体内可水解的酯：##STR1## 其中R.sup.1是氢，甲氧基或甲酰胺基；R.sup.2是酰基，特别是一种抗菌活性头孢菌素的酰基；CO.sub.2 R.sup.6是羧基或羧酸根离子；R.sup.4是丁烯内酯或丁醇内酯环，可选地被一个或两个烷基，二烷基氨基，烷氧基，羟基或芳基取代，这些基团可以相同或不同，或者其中两个相邻的可取代碳原子定义为芳香融合双环系统的共轭键；X是S，SO，SO.sub.2，O或CH.sub.2；虚线相邻于R.sup.4表示可选的双键。公开了用于制备化合物的过程以及用于其中的中间体。
• Cephalosporin compounds, process for their preparation and pharmaceutical compositions
  申请人：BEECHAM GROUP PLC

  公开号：EP0359536A2

  公开（公告）日：1990-03-21

  β-Lactam antibiotics of the formula (Ia) or a pharmaceutically acceptable salt or pharmaceutically acceptable in vivo hydrolysable ester thereof are disclosed: wherein R¹ is hydrogen, methoxy or formamido; R² is an acyl group, in particular that of an antibacterially active cephalosporin; CO₂R⁶ is a carboxy group or a carboxylate anion; R⁴ is a butenolide or butanolide ring, optionally substituted by one or two alkyl, dialkylamino, alkoxy, hydroxy, halogen or aryl groups, which may be the same or different, or, wherein two adjacent carbon atoms which are available for substitution define the common bond of an aromatic fused bicyclic system; X is S,SO,SO₂,O or CH₂; and the dashed line adjacent to R⁴ represents an optional double bond. Processes for the preparation of compounds together with intermediates for use therein are disclosed.

  本发明公开了式(Ia)的β-内酰胺类抗生素或其药学上可接受的盐或药学上可接受的体内可水解酯： 其中 R¹ 是氢、甲氧基或甲酰胺基； R² 是酰基，特别是抗菌活性头孢菌素的酰基； CO₂R⁶ 是羧基或羧酸阴离子； R⁴ 是丁烯内酯或丁内酯环，可选择被一个或两个烷基、二烷基氨基、烷氧基、羟基、卤素或芳基取代，这些基团可以是相同的或不同的，或者，其中两个相邻的碳原子可被取代，它们定义了芳香族融合双环系统的公共键； X 是 S、SO、SO₂、O 或 CH₂；R⁴ 旁的虚线代表任选双键。 本发明公开了化合物及其中间体的制备方法。
• Fell, Stephen C. M.; Pearson, Michael J.; Burton, George, Journal of the Chemical Society. Perkin transactions I, 1991, # 6, p. 1361 - 1364
  作者：Fell, Stephen C. M.、Pearson, Michael J.、Burton, George、Bateson, John H.

  DOI：——

  日期：——
• New β-Lactam-Antibiotics. Fluorinated Cephalosporins. Preliminary Communication. Modifikationen von Antibiotika. 15. Mitteilung
  作者：Beat Müller、Heinrich Peter、Peter Schneider、Hans Bickel

  DOI：10.1002/hlca.19750580826

  日期：1975.11.5

  AbstractNeue Cephalosporine, die in 3‐Stellung eine Fluormethylgruppe aufweisen (9, 17/Schema 1), wurden ausgehend von 2b unter Verwendung von 2‐Chlor‐1,1,2‐trifluor‐triäthylamin als Fluorierungsmittel hergestellt. Mit Piperidin‐schwefeltrifluorid erhielt man ferner aus 18 die 3‐Difluormethyl‐cephemverbindung 19 (Schema 2), die nach bekannten Methoden in antibakteriell wirksame Cephalosporine (20a, b) übergeführt wurde. 3‐Fluor‐cephemderivate, z.B. 23b, liessen sich ausgehend von entsprechenden 3‐Hydroxy‐cephemverbindungen, mit diesem Reagens jedoch nur in sehr geringer Ausbeute herstellen.
• Neue β-Lactam-Antibiotika. Cephem-Derivate mit elektronenanziehenden Substituenten in 3-Stellung. Modifikationen von Antibiotika. 14. Mitteilung
  作者：Heinrich Peter、Beat Müller、Hans Bickel

  DOI：10.1002/hlca.19750580825

  日期：1975.11.5

  New β‐lactam antibiotics. Cephem derivatives with electron withdrawing substituents at position 3Oxidation of the 3‐formyl‐2‐cephem compound 1 according to Corey [6] gave 2‐cephem‐3‐carboxylic esters 4a, b, c (Scheme 1), which proved to be useful intermediates for the synthesis of cephalosporins bearing in position 3 a methoxycarbonyl group (10a, b, c, d / Scheme 2) or a carboxy group (20, 25, 30/Schemes 3, 4). The 3‐formyl‐3‐cephem compounds 31a, b could be transformed into cyano‐ (33a) or methoxyiminomethyl‐ (36a, c, d) cephems (Scheme 5), which represent further examples of cephalosporins with electron withdrawing groups in position 3.