{(1S,6R)-6-Hydroxy-1-[(S)-hydroxy-((S)-2,2,4-trimethyl-[1,3]dioxolan-4-yl)-methyl]-8,10-dioxo-2-oxa-7,9-diaza-bicyclo[4.2.2]dec-5-yl}-acetic acid methyl ester | 202730-28-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: {(1S,6R)-6-Hydroxy-1-[(S)-hydroxy-((S)-2,2,4-trimethyl-[1,3]dioxolan-4-yl)-methyl]-8,10-dioxo-2-oxa-7,9-diaza-bicyclo[4.2.2]dec-5-yl}-acetic acid methyl ester
• CAS: 202730-28-7
• 化学式: C₁₇H₂₆N₂O₉
• 分子量: 402.401
• InChiKey: ZYYMNCBDHOCSRR-PNJWTBMTSA-N

反应信息

• 作为反应物：
  描述：

  {(1S,6R)-6-Hydroxy-1-[(S)-hydroxy-((S)-2,2,4-trimethyl-[1,3]dioxolan-4-yl)-methyl]-8,10-dioxo-2-oxa-7,9-diaza-bicyclo[4.2.2]dec-5-yl}-acetic acid methyl ester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以32%的产率得到(1S,6R)-6-Hydroxy-5-(2-hydroxy-ethyl)-1-[(S)-hydroxy-((S)-2,2,4-trimethyl-[1,3]dioxolan-4-yl)-methyl]-2-oxa-7,9-diaza-bicyclo[4.2.2]decane-8,10-dione
  参考文献：
  名称：

  5a-Methyl-Substituted Bicyclomycins:  Synthesis and Chemical, Biochemical, and Biological Properties

  摘要：

  A select series of 5a-methyl-substituted bicyclomycins (2-10, 34) have been prepared to identify interactions that influence antibiotic binding to the Escherichia coli rho transcription termination factor and to aid in identifying the bicyclomycin binding domain. The regioselective reduction of methyl 5a-bicyclomycincarboxylate C(2'), C(3')-acetonide (13) using lithium triethylborohydride provided 5a-(hydroxy)methylbicyclomycin C(2'),C(3')-acetonide (14). Alcohol 14 served as the key synthetic intermediate in preparing the targeted compounds. Replacing or modifying the terminal hydroxy group in 14 gave the corresponding hydrogen, acyl, halogen, azide, amine, and amide derivatives, which were then treated with trifluoroacetic acid to remove the C(2'),C(3')-acetonide protecting group to give 2-10. The chemical reactivity of 5a-(chloro)methylbicyclomycin (6) with the nucleophile EtSH was compared with bicyclomycin (1). We found that allylic chloride 6 underwent S(N)2 displacement with EtSH, while 1 furnished C(5)-C(5a) exomethylene group modified adducts. suggesting that Ci may serve as a site selective irreversible alkylation probe. Evaluation of 2-6, 8-10, and 34 in rho functional assays showed that 5a-methylbicydomycin (2), 5a-(hydroxy)methylbicyclomycin (3), 5a-[2,6-bis(trifluoromethyl)benzoxy]methylbicyclomycin (5), 5a-(azido)-methylbicyclomycin (8), 5a-(ethylmercapto)methylbicyclomycin (34), and 6 all exhibited inhibitory properties comparable with 1. The activities of these compounds and the remaining bicyclomycins within this series provided information of the structural interactions that occur with drug binding. Finally, we found that 2 displayed comparable antimicrobial activity with 1 in the filter disc assay. Compound 2 is the most biologically active bicyclomycin derivative reported to date.

  DOI：

  10.1021/jo972055y
• 作为产物：
  描述：

  [(1S,6R)-6-Hydroxy-8,10-dioxo-1-((1S,2S)-1,2,3-trihydroxy-2-methyl-propyl)-2-oxa-7,9-diaza-bicyclo[4.2.2]dec-(5E)-ylidene]-acetic acid methyl ester 在 palladium on activated charcoal 氢气 、 对甲苯磺酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.75h， 生成 {(1S,6R)-6-Hydroxy-1-[(S)-hydroxy-((S)-2,2,4-trimethyl-[1,3]dioxolan-4-yl)-methyl]-8,10-dioxo-2-oxa-7,9-diaza-bicyclo[4.2.2]dec-5-yl}-acetic acid methyl ester
  参考文献：
  名称：

  5a-Methyl-Substituted Bicyclomycins:  Synthesis and Chemical, Biochemical, and Biological Properties

  摘要：

  A select series of 5a-methyl-substituted bicyclomycins (2-10, 34) have been prepared to identify interactions that influence antibiotic binding to the Escherichia coli rho transcription termination factor and to aid in identifying the bicyclomycin binding domain. The regioselective reduction of methyl 5a-bicyclomycincarboxylate C(2'), C(3')-acetonide (13) using lithium triethylborohydride provided 5a-(hydroxy)methylbicyclomycin C(2'),C(3')-acetonide (14). Alcohol 14 served as the key synthetic intermediate in preparing the targeted compounds. Replacing or modifying the terminal hydroxy group in 14 gave the corresponding hydrogen, acyl, halogen, azide, amine, and amide derivatives, which were then treated with trifluoroacetic acid to remove the C(2'),C(3')-acetonide protecting group to give 2-10. The chemical reactivity of 5a-(chloro)methylbicyclomycin (6) with the nucleophile EtSH was compared with bicyclomycin (1). We found that allylic chloride 6 underwent S(N)2 displacement with EtSH, while 1 furnished C(5)-C(5a) exomethylene group modified adducts. suggesting that Ci may serve as a site selective irreversible alkylation probe. Evaluation of 2-6, 8-10, and 34 in rho functional assays showed that 5a-methylbicydomycin (2), 5a-(hydroxy)methylbicyclomycin (3), 5a-[2,6-bis(trifluoromethyl)benzoxy]methylbicyclomycin (5), 5a-(azido)-methylbicyclomycin (8), 5a-(ethylmercapto)methylbicyclomycin (34), and 6 all exhibited inhibitory properties comparable with 1. The activities of these compounds and the remaining bicyclomycins within this series provided information of the structural interactions that occur with drug binding. Finally, we found that 2 displayed comparable antimicrobial activity with 1 in the filter disc assay. Compound 2 is the most biologically active bicyclomycin derivative reported to date.

  DOI：

  10.1021/jo972055y