diphenylmethyl (4R)-6,6-dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate 4-oxide | 123285-25-6

• 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: diphenylmethyl (4R)-6,6-dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate 4-oxide
• 英文别名: benzhydryl 6,6-dibrompenicillinate sulfoxide；benzhydryl (2S,4R,5R)-6,6-dibromo-3,3-dimethyl-4,7-dioxo-4λ4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• CAS: 123285-25-6
• 化学式: C₂₁H₁₉Br₂NO₄S
• 分子量: 541.26
• InChiKey: KUCBNJSCRJWDNK-NXYYRJHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.68
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  diphenylmethyl (4R)-6,6-dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate 4-oxide 在 lead(II) bromide 、 氢化铝 作用下， 以 四氢呋喃 、 甲醇 、 氢溴酸 为溶剂， 反应 2.0h， 以93%的产率得到benzhydryl penicillinate 1α-oxide
  参考文献：
  名称：

  A Facile Reductive Removal of Bromine Atom(s) of 6,6-Dibromo- and 6-Bromopenicillanate Derivatives in a Pb/Al Bimetal System

  摘要：

  在含有 1% 的甲醇中，在催化量的溴化铅 (II) 存在下，用金属铝处理，成功还原去除了 6,6-二溴- 和 6-溴青霉烷酸 1-氧化物中的溴原子氢溴酸水溶液。以类似的方式，6,6-二溴青霉烷酸酯及其1,1-二氧化物可以分别转化为相应的脱溴产物。

  DOI：

  10.1246/bcsj.62.627
• 作为产物：
  描述：

  diphenylmethyl 6,6-dibromopenicillanate 在 2,2-dimethyldioxirane 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 0.17h， 生成 diphenylmethyl (4R)-6,6-dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate 4-oxide
  参考文献：
  名称：

  使用二甲基二环氧乙烷将青霉素衍生物选择性氧化为青霉素（1R）和（1S）-亚砜

  摘要：

  我们描述了通过相应的青霉酸酯和二甲基二环氧乙烷烷不对称氧化制备（1R）-6,6-二卤代-，6β-卤代青霉酸酯，6,6-二卤代戊酰胺衍生物和（1S）-6-α-卤代青酸酯亚砜的便捷程序戊烷衍生物。该方法的特点是反应条件温和，反应时间短，选择性好，产率极高，反应后处理容易并且完全避免了过氧化产物的产生。

  DOI：

  10.1016/s0040-4039(00)61499-5

文献信息

• Chemoselective aerobic oxidation of penicillin and cephalosporin derivatives into sulfoxides
  作者：Hideo Tanaka、Ryo Kikuchi、Sigeru Torii

  DOI：10.1016/0040-4020(95)01075-0

  日期：1996.2

  Aerobic oxidation of penicillin and cephalosporin derivatives in the presence of cobalt(III) acetylacetonate and an aldehyde under oxygen atmosphere took place in a chemoselective manner to afford the corresponding sulfoxides, exclusively.

  在氧气气氛下，在乙酰丙酮钴（III）和醛存在下，以化学选择性方式对青霉素和头孢菌素衍生物进行有氧氧化，从而仅得到相应的亚砜。
• Rational Design of a β-Lactamase Inhibitor Achieved via Stabilization of the <i>trans</i>-Enamine Intermediate:  1.28 Å Crystal Structure of <i>wt</i> SHV-1 Complex with a Penam Sulfone
  作者：Pius S. Padayatti、Anjaneyulu Sheri、Monica A. Totir、Marion S. Helfand、Marianne P. Carey、Vernon E. Anderson、Paul R. Carey、Christopher R. Bethel、Robert A. Bonomo、John D. Buynak、Focco van den Akker

  DOI：10.1021/ja063715w

  日期：2006.10.1

  beta-Lactamases are one of the major causes of antibiotic resistance in Gram negative bacteria. The continuing evolution of beta-lactamases that are capable of hydrolyzing our most potent beta-lactams presents a vexing clinical problem, in particular since a number of them are resistant to inhibitors. The efficient inhibition of these enzymes is therefore of great clinical importance. Building upon our previous structural studies that examined tazobactam trapped as a trans-enamine intermediate in a deacylation deficient SHV variant, we designed a novel penam sulfone derivative that forms a more stable trans-enamine intermediate. We report here the 1.28 A resolution crystal structure of wt SHV-1 in complex with a rationally designed penam sulfone, SA2-13. The compound is covalently bound to the active site of wt SHV-1 similar to tazobactam yet forms an additional salt-bridge with K234 and hydrogen bonds with S130 and T235 to stabilize the trans-enamine intermediate. Kinetic measurements show that SA2-13, once reacted with SHV-1 beta-lactamase, is about 10-fold slower at being released from the enzyme compared to tazobactam. Stabilizing the trans-enamine intermediate represents a novel strategy for the rational design of mechanism-based class A beta-lactamase inhibitors.