(3Z,5E,7R,9S,11E,13E,15S,16R)-16-[(2S,3R,4S)-3-hydroxy-4-[(2R,5R,6R)-2-hydroxy-5-methyl-4-oxo-6-propan-2-yloxan-2-yl]pentan-2-yl]-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraene-2,8-dione | 181464-42-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (3Z,5E,7R,9S,11E,13E,15S,16R)-16-[(2S,3R,4S)-3-hydroxy-4-[(2R,5R,6R)-2-hydroxy-5-methyl-4-oxo-6-propan-2-yloxan-2-yl]pentan-2-yl]-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraene-2,8-dione
• CAS: 181464-42-6
• 化学式: C₃₅H₅₄O₉
• 分子量: 618.808
• InChiKey: LSTPCZYIRREGRC-PHYYHISYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  44
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (3Z,5E,7R,9S,11E,13E,15S,16R)-16-[(2S,3R,4S)-3-hydroxy-4-[(2R,5R,6R)-2-hydroxy-5-methyl-4-oxo-6-propan-2-yloxan-2-yl]pentan-2-yl]-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraene-2,8-dione 在 ammonium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 33.0h， 生成 (2S,3R,4S)-4-((4E,6E,12E,14Z)-(2R,3S,9S,11R)-3,15-Dimethoxy-7,9,11,13-tetramethyl-10,16-dioxo-oxacyclohexadeca-4,6,12,14-tetraen-2-yl)-3-hydroxy-2-methyl-pentanoic acid methyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Bafilomycin A₁ Derivatives as Inhibitors of Vacuolar H⁺-ATPase

  摘要：

  The macrolide antibiotic bafilomycin A(1) is a highly potent and selective inhibitor of all the vacuolar ATPases (V-ATPases). With the aim of obtaining novel analogues specific for the osteoclast subclass of vacuolar ATPase, 31 derivatives of bafilomycin A(1) were synthesized and tested for their ability to inhibit differentially the V-ATPase-driven proton transport in membrane vesicles derived from chicken osteoclasts (cOc) and bovine chromaffin granules (bCG). Although none of the new analogues were more potent than the parent compound, the obtained data provided a significant amount of information about the structural requirements for the inhibitory activity of bafilomycin A(1). The different effects of a few analogues on the two enzymes could also suggest the possibility of a selective modulation of the V-ATPases in different tissues.

  DOI：

  10.1021/jm9707838
• 作为产物：
  描述：

  巴佛洛霉素A1 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以100%的产率得到(3Z,5E,7R,9S,11E,13E,15S,16R)-16-[(2S,3R,4S)-3-hydroxy-4-[(2R,5R,6R)-2-hydroxy-5-methyl-4-oxo-6-propan-2-yloxan-2-yl]pentan-2-yl]-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraene-2,8-dione
  参考文献：
  名称：

  Bafilomycin A（1）羟基的选择性氧化。

  摘要：

  DOI：

  10.1021/jo9607222

文献信息

• Structure–Activity Relationships of Natural and Semisynthetic Plecomacrolides Suggest Distinct Pathways for HIV-1 Immune Evasion and Vacuolar ATPase-Dependent Lysosomal Acidification
  作者：Morgan McCauley、Matthew Huston、Alanna R. Condren、Filipa Pereira、Joel Cline、Marianne Yaple-Maresh、Mark M. Painter、Gretchen E. Zimmerman、Andrew W. Robertson、Nolan Carney、Christopher Goodall、Valeri Terry、Rolf Müller、David H. Sherman、Kathleen L. Collins

  DOI：10.1021/acs.jmedchem.3c01574

  日期：2024.3.28

  acidification or degradation. We conducted a structure–activity relationship study that assessed 76 compounds for Nef inhibition, 24 and 72 h viability, and lysosomal neutralization in Nef-expressing primary T cells. This analysis demonstrated that the most potent compounds were natural concanamycins and their derivatives. Comparison against a set of new, semisynthetic concanamycins revealed that substituents

  人类免疫缺陷病毒 (HIV) 编码的辅助蛋白 Nef 通过减少主要组织相容性复合物 I (MHC-I) 细胞表面表达来增强致病性，保护 HIV 感染细胞免受免疫识别。 MHC-I 的 Nef 依赖性下调可以通过亚纳摩尔浓度的刀刀霉素 A ( 1 ) 逆转，刀刀霉素 A 是一种众所周知的液泡 ATP 酶抑制剂，浓度低于干扰溶酶体酸化或降解的浓度。我们进行了一项结构-活性关系研究，评估了 76 种化合物对表达 Nef 的原代 T 细胞的 Nef 抑制、24 和 72 小时活力以及溶酶体中和作用。该分析表明，最有效的化合物是天然刀那霉素及其衍生物。与一组新的半合成刀刀霉素的比较表明，C-8 的取代基和 C-9 的酰化显着影响 Nef 效力、靶细胞活力和溶酶体中和。这些发现为了解这些化合物的作用机制和鉴定先进的先导抗 HIV Nef 抑制化合物提供了重要进展。
• Synthesis and Structure−Activity Relationships of Bafilomycin A₁ Derivatives as Inhibitors of Vacuolar H⁺-ATPase
  作者：Stefania Gagliardi、P. Andrea Gatti、Pietro Belfiore、Andrea Zocchetti、Geoffrey D. Clarke、Carlo Farina

  DOI：10.1021/jm9707838

  日期：1998.5.1

  The macrolide antibiotic bafilomycin A(1) is a highly potent and selective inhibitor of all the vacuolar ATPases (V-ATPases). With the aim of obtaining novel analogues specific for the osteoclast subclass of vacuolar ATPase, 31 derivatives of bafilomycin A(1) were synthesized and tested for their ability to inhibit differentially the V-ATPase-driven proton transport in membrane vesicles derived from chicken osteoclasts (cOc) and bovine chromaffin granules (bCG). Although none of the new analogues were more potent than the parent compound, the obtained data provided a significant amount of information about the structural requirements for the inhibitory activity of bafilomycin A(1). The different effects of a few analogues on the two enzymes could also suggest the possibility of a selective modulation of the V-ATPases in different tissues.
• Selective Oxidation of Hydroxy Groups of Bafilomycin A₁
  作者：Pier Andrea Gatti、Stefania Gagliardi、Alberto Cerri、Marco Visconti、Carlo Farina

  DOI：10.1021/jo9607222

  日期：1996.1.1