diphenylmethyl N-carbethoxy-S-aminosulfeniminopenicillanate | 216007-05-5

• 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 N-carbethoxy-S-aminosulfeniminopenicillanate
• 英文别名: benzhydryl (2S,5R)-6-(ethoxycarbonylamino)sulfanylimino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• CAS: 216007-05-5
• 化学式: C₂₄H₂₅N₃O₅S₂
• 分子量: 499.612
• InChiKey: ZLSMDVGZKJURBH-PZJWPPBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  148
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diphenylmethyl N-carbethoxy-S-aminosulfeniminopenicillanate 在 三氯化铝 、 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 反应 0.25h， 生成 sodium N-carbethoxy-S-aminosulfeniminopenicillanate-1-sulfoxide
  参考文献：
  名称：

  S-Aminosulfeniminopenicillins:  Multimode β-Lactamase Inhibitors and Template Structures for Penicillin-Based β-Lactamase Substrates as Prodrugs

  摘要：

  A series of novel penicillins, bearing an S-aminosulfenimine (R'(R ")NSN=) side chain at the 6-position, have been prepared by direct reaction of a penicillin eater with sulfur diimides. A set of these structures, with the thiazolidine-ring sulfur in the sulfide oxidation state, exhibited a pattern of reactivity not previously encountered in penicillin chemistry, viz., cleavage of the beta-lactam ring resulted in a rapid intramolecular displacement of the S-amino moiety as R'(R ")NH. This was found to be the exclusive reaction occurring consequent on cleavage of the p-lactam ring. The mechanism of this process was delineated in a detailed study in basic methanol. That a similar reactivity pattern held for a penicillin salt in aqueous solution was also verified. Thus the salt 5bm (R' = CH3, R " = p-CH3C6H4SO2) behaved as a moderate substrate for beta-lactamase type I from Bacillus cereus (k(cat)/K-m = 6.26 x 10(5) M-1 min(-1)). On enzyme-catalyzed hydrolysis of this compound, displacement of N-methyl-p-toluenesulfonamide (R'(R ")NH) was directly observed (H-1 NMR) and found to occur faster than displacement of this group from (intact) 5bm in aqueous buffer, by a factor of at least 600. These findings identified the potential of the S-aminosulfeniminopenicillin structure type to be developed as beta-lactamase substrates for use as site-specific-release prodrugs. A degree of enzyme inhibition was also observed with this set of thiazolidinering-sulfide structures with the most potent inhibitor having the most nucleofugic S-amino moiety p-ClC6H4SO2N(CH3), indicating that displacement of this group, at the enzyme active site, played a role in their mode of inhibition. Structures with the thiazolidine-ring sulfur in the sulfone oxidation state were considerably more potent as inhibitors, with the structure 5a(2) being the most active. As this compound bore the least nucleofugic S-amino moiety C2H5OC(O)NH, it indicated that the mode of inhibition of the sulfones was distinct from that of the thiazolidine-ring sulfides; it is probable that the sulfones reacted in a manner similar to that shown by sulbactam viz., rapid scission of the thiazolidine-sulfone ring after cleavage of the beta-lactam ring. Synergy of action was observed with 5a(2) at high concentration (78 mu g/mL) against Escherichia coli when combined 1:1 with penicillin G; no synergy was observed at low concentration (4 mu g/mL) when combined with pipericillin, indicating poor permeation characteristics.

  DOI：

  10.1021/jo970737f
• 作为产物：
  描述：

  N,N'-bis(ethoxycarbonyl) sulfur diimide 、 benzhydryl 6-aminopenicillanate 以 二氯甲烷 为溶剂， 反应 0.17h， 以48%的产率得到diphenylmethyl N-carbethoxy-S-aminosulfeniminopenicillanate
  参考文献：
  名称：

  S-Aminosulfeniminopenicillins:  Multimode β-Lactamase Inhibitors and Template Structures for Penicillin-Based β-Lactamase Substrates as Prodrugs

  摘要：

  A series of novel penicillins, bearing an S-aminosulfenimine (R'(R ")NSN=) side chain at the 6-position, have been prepared by direct reaction of a penicillin eater with sulfur diimides. A set of these structures, with the thiazolidine-ring sulfur in the sulfide oxidation state, exhibited a pattern of reactivity not previously encountered in penicillin chemistry, viz., cleavage of the beta-lactam ring resulted in a rapid intramolecular displacement of the S-amino moiety as R'(R ")NH. This was found to be the exclusive reaction occurring consequent on cleavage of the p-lactam ring. The mechanism of this process was delineated in a detailed study in basic methanol. That a similar reactivity pattern held for a penicillin salt in aqueous solution was also verified. Thus the salt 5bm (R' = CH3, R " = p-CH3C6H4SO2) behaved as a moderate substrate for beta-lactamase type I from Bacillus cereus (k(cat)/K-m = 6.26 x 10(5) M-1 min(-1)). On enzyme-catalyzed hydrolysis of this compound, displacement of N-methyl-p-toluenesulfonamide (R'(R ")NH) was directly observed (H-1 NMR) and found to occur faster than displacement of this group from (intact) 5bm in aqueous buffer, by a factor of at least 600. These findings identified the potential of the S-aminosulfeniminopenicillin structure type to be developed as beta-lactamase substrates for use as site-specific-release prodrugs. A degree of enzyme inhibition was also observed with this set of thiazolidinering-sulfide structures with the most potent inhibitor having the most nucleofugic S-amino moiety p-ClC6H4SO2N(CH3), indicating that displacement of this group, at the enzyme active site, played a role in their mode of inhibition. Structures with the thiazolidine-ring sulfur in the sulfone oxidation state were considerably more potent as inhibitors, with the structure 5a(2) being the most active. As this compound bore the least nucleofugic S-amino moiety C2H5OC(O)NH, it indicated that the mode of inhibition of the sulfones was distinct from that of the thiazolidine-ring sulfides; it is probable that the sulfones reacted in a manner similar to that shown by sulbactam viz., rapid scission of the thiazolidine-sulfone ring after cleavage of the beta-lactam ring. Synergy of action was observed with 5a(2) at high concentration (78 mu g/mL) against Escherichia coli when combined 1:1 with penicillin G; no synergy was observed at low concentration (4 mu g/mL) when combined with pipericillin, indicating poor permeation characteristics.

  DOI：

  10.1021/jo970737f

文献信息

• <i>S</i>-Aminosulfeniminopenicillins:  Multimode β-Lactamase Inhibitors and Template Structures for Penicillin-Based β-Lactamase Substrates as Prodrugs
  作者：Timothy P. Smyth、Michael E. O'Donnell、Michael J. O'Conno、James O. St Ledger

  DOI：10.1021/jo970737f

  日期：1998.10.1

  A series of novel penicillins, bearing an S-aminosulfenimine (R'(R ")NSN=) side chain at the 6-position, have been prepared by direct reaction of a penicillin eater with sulfur diimides. A set of these structures, with the thiazolidine-ring sulfur in the sulfide oxidation state, exhibited a pattern of reactivity not previously encountered in penicillin chemistry, viz., cleavage of the beta-lactam ring resulted in a rapid intramolecular displacement of the S-amino moiety as R'(R ")NH. This was found to be the exclusive reaction occurring consequent on cleavage of the p-lactam ring. The mechanism of this process was delineated in a detailed study in basic methanol. That a similar reactivity pattern held for a penicillin salt in aqueous solution was also verified. Thus the salt 5bm (R' = CH3, R " = p-CH3C6H4SO2) behaved as a moderate substrate for beta-lactamase type I from Bacillus cereus (k(cat)/K-m = 6.26 x 10(5) M-1 min(-1)). On enzyme-catalyzed hydrolysis of this compound, displacement of N-methyl-p-toluenesulfonamide (R'(R ")NH) was directly observed (H-1 NMR) and found to occur faster than displacement of this group from (intact) 5bm in aqueous buffer, by a factor of at least 600. These findings identified the potential of the S-aminosulfeniminopenicillin structure type to be developed as beta-lactamase substrates for use as site-specific-release prodrugs. A degree of enzyme inhibition was also observed with this set of thiazolidinering-sulfide structures with the most potent inhibitor having the most nucleofugic S-amino moiety p-ClC6H4SO2N(CH3), indicating that displacement of this group, at the enzyme active site, played a role in their mode of inhibition. Structures with the thiazolidine-ring sulfur in the sulfone oxidation state were considerably more potent as inhibitors, with the structure 5a(2) being the most active. As this compound bore the least nucleofugic S-amino moiety C2H5OC(O)NH, it indicated that the mode of inhibition of the sulfones was distinct from that of the thiazolidine-ring sulfides; it is probable that the sulfones reacted in a manner similar to that shown by sulbactam viz., rapid scission of the thiazolidine-sulfone ring after cleavage of the beta-lactam ring. Synergy of action was observed with 5a(2) at high concentration (78 mu g/mL) against Escherichia coli when combined 1:1 with penicillin G; no synergy was observed at low concentration (4 mu g/mL) when combined with pipericillin, indicating poor permeation characteristics.