(1S,5R,6R)-5,6-Dihydroxy-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 | 165605-76-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S,5R,6R)-5,6-Dihydroxy-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
• 英文别名: (1S,5R,6R)-5,6-dihydroxy-1-[(S)-hydroxy-[(4S)-2,2,4-trimethyl-1,3-dioxolan-4-yl]methyl]-2-oxa-7,9-diazabicyclo[4.2.2]decane-8,10-dione
• CAS: 165605-76-5
• 化学式: C₁₄H₂₂N₂O₈
• 分子量: 346.337
• InChiKey: SSHTZKKEKOKGDY-VIUKWPJHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  147
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1S,5R,6R)-5,6-Dihydroxy-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 在 硫酸 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以47%的产率得到8,10-Diaza-5,6-dihydroxy-1-(2-methyl-1,2,3-trihydroxypropyl)-2-oxabicyclo[4.2.2]decane-7,9-dione
  参考文献：
  名称：

  Bicyclomycin Oxidative Transformations. Synthesis and Chemical Properties of Bicyclomycin-5-norketone

  摘要：

  DOI：

  10.1021/jo00121a069
• 作为产物：
  描述：

  dihydrobicyclomycin 2',3'-acetonide 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 臭氧 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 生成 (1S,5R,6R)-5,6-Dihydroxy-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：

  Design, Syntheses, and Evaluations of Bicyclomycin-Based Rho Inactivators

  摘要：

  The commercial antibiotic bicyclomycin (1) has been shown to target the essential transcriptional termination factor rho in Escherichia coli. Little is known, however, about the bicyclomycin binding site in rho. A recent structure-activity relationship study permitted us to design modified bicyclomycins that may irreversibly inactivate rho. The four compounds selected were C(5a)-(4-azidoanilino)dihydrabicyclomycin (3), C(5a)-(3-formylanilino)dihydrobicyclomycin (4), C(5)-norbicyclomycin C(5)-O-(4-azidobenzoate) (5), and C(5)-norbicyclomycin C(5)-O-(3-formylbenzoate) (6). In each of these compounds the inactivating unit was placed at the C(5)-C(5a) site in bicyclomycin. In compounds 3 and 5 an aryl azide moiety was used as; a photoaffinity label whereas in 4 and 6 an aryl aldehyde group was employed as a reductive amination probe. The synthesis and spectral properties of 3-6 are described. Chemical studies demonstrated that 3 and 4 were stable in D2O and CD3OD (room temperature, 7 d), while 5 and 6 underwent significant change within 1 d. Biochemical investigations showed that 3 and 4 retained appreciable inhibitory activities in rho-dependent ATPase and transcription termination assays. In the ATPase assay, I-50 values for 1, 3, and 4 were 60, 135, and 70 mu M, respectively. Correspondingly, the I-50 values for 5 and 6 were > 400 and 225 mu M, respectively. In the transcription termination assay, compounds 1, 3, and 4 all prevented (greater than or equal to 97%) the production of rho-dependent transcripts at 40 mu M, whereas little (less than or equal to 15%) inhibition of transcription termination was observed for 5 and 6 at this concentration. Antimicrobial evaluation of 3-6 showed that none of the four compounds exhibited antibiotic activity at 32 mg/mL or less against W3350 E. coli. The combined chemical and biochemical studies led to our further evaluation of 3 and 4. Photochemical irradiation (254 nm) of 3 in the presence of rho led to a 29-32% loss of rho ATPase activity. Attempts to confirm the irreversible adduction of 3 to rho by electrospray mass spectrometry were unsuccessful, No higher molecular weight adducts were detected. Incubation of rho with 4 at room temperature (4 h) followed by the addition of NaBH4 led to significant losses (>62%) of rho ATPase activity. Analyses of the 4-rho modified adduct showed appreciable levels of adduction (similar to 40%). Mass spectrometric analyses indicated a molecular weight for the adduct of approximately 47 410, consistent with a modification of a rho lysine residue by 4. Compound 4 was selected for additional studies.

  DOI：

  10.1021/jo970575n

文献信息

• Design, Syntheses, and Evaluations of Bicyclomycin-Based Rho Inactivators
  作者：Hangjin Cho、Hyeung-geun Park、Xiangdong Zhang、Isabel Riba、Simon J. Gaskell、William R. Widger、Harold Kohn

  DOI：10.1021/jo970575n

  日期：1997.8.1

  The commercial antibiotic bicyclomycin (1) has been shown to target the essential transcriptional termination factor rho in Escherichia coli. Little is known, however, about the bicyclomycin binding site in rho. A recent structure-activity relationship study permitted us to design modified bicyclomycins that may irreversibly inactivate rho. The four compounds selected were C(5a)-(4-azidoanilino)dihydrabicyclomycin (3), C(5a)-(3-formylanilino)dihydrobicyclomycin (4), C(5)-norbicyclomycin C(5)-O-(4-azidobenzoate) (5), and C(5)-norbicyclomycin C(5)-O-(3-formylbenzoate) (6). In each of these compounds the inactivating unit was placed at the C(5)-C(5a) site in bicyclomycin. In compounds 3 and 5 an aryl azide moiety was used as; a photoaffinity label whereas in 4 and 6 an aryl aldehyde group was employed as a reductive amination probe. The synthesis and spectral properties of 3-6 are described. Chemical studies demonstrated that 3 and 4 were stable in D2O and CD3OD (room temperature, 7 d), while 5 and 6 underwent significant change within 1 d. Biochemical investigations showed that 3 and 4 retained appreciable inhibitory activities in rho-dependent ATPase and transcription termination assays. In the ATPase assay, I-50 values for 1, 3, and 4 were 60, 135, and 70 mu M, respectively. Correspondingly, the I-50 values for 5 and 6 were > 400 and 225 mu M, respectively. In the transcription termination assay, compounds 1, 3, and 4 all prevented (greater than or equal to 97%) the production of rho-dependent transcripts at 40 mu M, whereas little (less than or equal to 15%) inhibition of transcription termination was observed for 5 and 6 at this concentration. Antimicrobial evaluation of 3-6 showed that none of the four compounds exhibited antibiotic activity at 32 mg/mL or less against W3350 E. coli. The combined chemical and biochemical studies led to our further evaluation of 3 and 4. Photochemical irradiation (254 nm) of 3 in the presence of rho led to a 29-32% loss of rho ATPase activity. Attempts to confirm the irreversible adduction of 3 to rho by electrospray mass spectrometry were unsuccessful, No higher molecular weight adducts were detected. Incubation of rho with 4 at room temperature (4 h) followed by the addition of NaBH4 led to significant losses (>62%) of rho ATPase activity. Analyses of the 4-rho modified adduct showed appreciable levels of adduction (similar to 40%). Mass spectrometric analyses indicated a molecular weight for the adduct of approximately 47 410, consistent with a modification of a rho lysine residue by 4. Compound 4 was selected for additional studies.
• Bicyclomycin Oxidative Transformations. Synthesis and Chemical Properties of Bicyclomycin-5-norketone
  作者：Zhuming Zhang、Hyeung-guen Park、Harold Kohn

  DOI：10.1021/jo00121a069

  日期：1995.8