(3R,4S)-3-hydroxy-4-[(2S,3R)-3-hydroxy-4-oxo-1-[(1S)-1-phenylethyl]azetidin-2-yl]-1-[(1S)-1-phenylethyl]azetidin-2-one | 183066-59-3

• 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: (3R,4S)-3-hydroxy-4-[(2S,3R)-3-hydroxy-4-oxo-1-[(1S)-1-phenylethyl]azetidin-2-yl]-1-[(1S)-1-phenylethyl]azetidin-2-one
• CAS: 183066-59-3
• 化学式: C₂₂H₂₄N₂O₄
• 分子量: 380.444
• InChiKey: WGJJWBJVCOLBGE-LLTUXKBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  硫酸二甲酯 、 (3R,4S)-3-hydroxy-4-[(2S,3R)-3-hydroxy-4-oxo-1-[(1S)-1-phenylethyl]azetidin-2-yl]-1-[(1S)-1-phenylethyl]azetidin-2-one 在 sodium hydroxide 、 四丁基碘化铵 作用下， 以 二氯甲烷 为溶剂， 以91%的产率得到(3R,4S)-3-methoxy-4-[(2S,3R)-3-methoxy-4-oxo-1-[(1S)-1-phenylethyl]azetidin-2-yl]-1-[(1S)-1-phenylethyl]azetidin-2-one
  参考文献：
  名称：

  C4,C4‘-Bis-β-lactam to Fused Bis-γ-lactam Rearrangement

  摘要：

  Optically pure cis,cis-C4,C4'-bis-beta-lactams 1a-d are obtained in good to excellent yields, in a single step, following two different approaches. Staudinger reaction of (S)-(4-phenyl-2-oxooxazolidinyl)acetyl chloride (2a) and p-anisyldiimine gave the corresponding bis-beta-lactam la as a single enantiomer. The reaction of glyoxal diimine derived from (S)-alpha-phenylethylamine and different alkoxy-substituted acid chlorides gave diastereomeric mixtures of cis,cis-bis-beta-lactams 1b-d, enantiomers at the bicyclic skeleton. The configuration of all compounds has been determined by X-ray diffraction analysis of enantiomerically pure aldehyde 4a and bis-beta-lactam Ib-a. The remaining bicyclic lactams have been chemically correlated to compound 1b-alpha and their configurations assigned. Starting from enantiomerically pure 4-formyl-2-azetidinone 4b, sequential imine formation and ketene cycloaddition allowed the synthesis of differently substituted, optically pure cis,cis-C4,C4'-bis-beta-lactams If-i in good overall yields. C4,C4'-Bis-beta-lactams smoothly rearranged to fused trans,trans-bis-gamma-lactams 7 upon basic treatment (NaOMe/MeOH) in a totally stereoselective process. The presence of alkyl groups attached to the lactam nitrogen inhibits the rearrangement. Differently substituted (aryl and alkyl substituents in either rings) bicyclic p-lactam systems gave the selective opening of the ring with the aromatic substituent attached to the lactam nitrogen. Monocyclic 2-azetidinones 8 with an amino ester side chain at C4 are then obtained. The synthesis of trans,cis-C4,C4'-bis-beta-lactam Ij and trans,trans-C4,C4'-bis-beta-lactam 11 has also been effected in the racemic form. Compound Ij with a trans,cis stereochemistry rearranged to cis,trans-bis-gamma-lactam 7d in the presence of base while the trans,trans-bicycle 11 gave monocyclic 2-azetidinone 8c with an amino ester side chain. Finally, trans,trans-bis-gamma-lactam 11 can be synthesized in a single step from glyoxal diimine 3a employing an excess of lithium isovalerate. A reaction pathway to account for all the observed data is proposed.

  DOI：

  10.1021/jo960826c
• 作为产物：
  描述：

  [(2S,3R)-2-[(2S,3R)-3-acetyloxy-4-oxo-1-[(1S)-1-phenylethyl]azetidin-2-yl]-4-oxo-1-[(1S)-1-phenylethyl]azetidin-3-yl] acetate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以81%的产率得到(3R,4S)-3-hydroxy-4-[(2S,3R)-3-hydroxy-4-oxo-1-[(1S)-1-phenylethyl]azetidin-2-yl]-1-[(1S)-1-phenylethyl]azetidin-2-one
  参考文献：
  名称：

  C4,C4‘-Bis-β-lactam to Fused Bis-γ-lactam Rearrangement

  摘要：

  Optically pure cis,cis-C4,C4'-bis-beta-lactams 1a-d are obtained in good to excellent yields, in a single step, following two different approaches. Staudinger reaction of (S)-(4-phenyl-2-oxooxazolidinyl)acetyl chloride (2a) and p-anisyldiimine gave the corresponding bis-beta-lactam la as a single enantiomer. The reaction of glyoxal diimine derived from (S)-alpha-phenylethylamine and different alkoxy-substituted acid chlorides gave diastereomeric mixtures of cis,cis-bis-beta-lactams 1b-d, enantiomers at the bicyclic skeleton. The configuration of all compounds has been determined by X-ray diffraction analysis of enantiomerically pure aldehyde 4a and bis-beta-lactam Ib-a. The remaining bicyclic lactams have been chemically correlated to compound 1b-alpha and their configurations assigned. Starting from enantiomerically pure 4-formyl-2-azetidinone 4b, sequential imine formation and ketene cycloaddition allowed the synthesis of differently substituted, optically pure cis,cis-C4,C4'-bis-beta-lactams If-i in good overall yields. C4,C4'-Bis-beta-lactams smoothly rearranged to fused trans,trans-bis-gamma-lactams 7 upon basic treatment (NaOMe/MeOH) in a totally stereoselective process. The presence of alkyl groups attached to the lactam nitrogen inhibits the rearrangement. Differently substituted (aryl and alkyl substituents in either rings) bicyclic p-lactam systems gave the selective opening of the ring with the aromatic substituent attached to the lactam nitrogen. Monocyclic 2-azetidinones 8 with an amino ester side chain at C4 are then obtained. The synthesis of trans,cis-C4,C4'-bis-beta-lactam Ij and trans,trans-C4,C4'-bis-beta-lactam 11 has also been effected in the racemic form. Compound Ij with a trans,cis stereochemistry rearranged to cis,trans-bis-gamma-lactam 7d in the presence of base while the trans,trans-bicycle 11 gave monocyclic 2-azetidinone 8c with an amino ester side chain. Finally, trans,trans-bis-gamma-lactam 11 can be synthesized in a single step from glyoxal diimine 3a employing an excess of lithium isovalerate. A reaction pathway to account for all the observed data is proposed.

  DOI：

  10.1021/jo960826c

文献信息

• C4,C4‘-Bis-β-lactam to Fused Bis-γ-lactam Rearrangement
  作者：Benito Alcaide、Yolanda Martín-Cantalejo、Javier Pérez-Castells、Miguel A. Sierra、Angeles Monge

  DOI：10.1021/jo960826c

  日期：1996.1.1

  Optically pure cis,cis-C4,C4'-bis-beta-lactams 1a-d are obtained in good to excellent yields, in a single step, following two different approaches. Staudinger reaction of (S)-(4-phenyl-2-oxooxazolidinyl)acetyl chloride (2a) and p-anisyldiimine gave the corresponding bis-beta-lactam la as a single enantiomer. The reaction of glyoxal diimine derived from (S)-alpha-phenylethylamine and different alkoxy-substituted acid chlorides gave diastereomeric mixtures of cis,cis-bis-beta-lactams 1b-d, enantiomers at the bicyclic skeleton. The configuration of all compounds has been determined by X-ray diffraction analysis of enantiomerically pure aldehyde 4a and bis-beta-lactam Ib-a. The remaining bicyclic lactams have been chemically correlated to compound 1b-alpha and their configurations assigned. Starting from enantiomerically pure 4-formyl-2-azetidinone 4b, sequential imine formation and ketene cycloaddition allowed the synthesis of differently substituted, optically pure cis,cis-C4,C4'-bis-beta-lactams If-i in good overall yields. C4,C4'-Bis-beta-lactams smoothly rearranged to fused trans,trans-bis-gamma-lactams 7 upon basic treatment (NaOMe/MeOH) in a totally stereoselective process. The presence of alkyl groups attached to the lactam nitrogen inhibits the rearrangement. Differently substituted (aryl and alkyl substituents in either rings) bicyclic p-lactam systems gave the selective opening of the ring with the aromatic substituent attached to the lactam nitrogen. Monocyclic 2-azetidinones 8 with an amino ester side chain at C4 are then obtained. The synthesis of trans,cis-C4,C4'-bis-beta-lactam Ij and trans,trans-C4,C4'-bis-beta-lactam 11 has also been effected in the racemic form. Compound Ij with a trans,cis stereochemistry rearranged to cis,trans-bis-gamma-lactam 7d in the presence of base while the trans,trans-bicycle 11 gave monocyclic 2-azetidinone 8c with an amino ester side chain. Finally, trans,trans-bis-gamma-lactam 11 can be synthesized in a single step from glyoxal diimine 3a employing an excess of lithium isovalerate. A reaction pathway to account for all the observed data is proposed.