(9S)-9-dihydro-9,11-O-isopropylideneerythronolide A | 138505-34-7

• 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: (9S)-9-dihydro-9,11-O-isopropylideneerythronolide A
• 英文别名: (1R,2R,3R,6R,7S,8S,9R,10R,12R,13S,17S)-3-ethyl-2,7,9,10-tetrahydroxy-2,6,8,10,12,15,15,17-octamethyl-4,14,16-trioxabicyclo[11.3.1]heptadecan-5-one
• CAS: 138505-34-7
• 化学式: C₂₄H₄₄O₈
• 分子量: 460.609
• InChiKey: HROJPOWTALZERH-SIYRFQEZSA-N

物化性质

• 沸点：
  597.3±50.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  32
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (9S)-9-dihydro-9,11-O-isopropylideneerythronolide A 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 23.33h， 生成 (9S)-9-dihydro-9,11-O-isopropylidene-3-O-((4-(N-methylcarbamoylguanidyl)butyl)carbamoyl)-5-O-propargylerythronolide A
  参考文献：
  名称：

  Creation of Customized Bioactivity within a 14-Membered Macrolide Scaffold: Design, Synthesis, and Biological Evaluation Using a Family-18 Chitinase

  摘要：

  Argifin, a 17-membered pentapeptide, inhibits chitinase. As argifin has properties that render it unsuitable as a drug development candidate, we devised a mechanism to create the structural component of argifin that bestows the chitinase inhibition and introduce it into a 14-membered macrolide scaffold. Here we describe (1) the designed macrolide, which exhibits similar to 200-fold more potent chitinase inhibition than argifin, (2) the binding modes of the macrolide with Serratia marcescens chitinase B, and (3) the computed analysis explaining the reason for derivatives displaying increased inhibition compared to argifin, the macrolide aglycone displaying inhibition in a nanomolar range. This promises a class of chitinase inhibitors with novel skeletons, providing innovative insight for drug design and the use of macrolides as adaptable, flexible templates for use in drug discovery research and development.

  DOI：

  10.1021/acs.jmedchem.5b00175
• 作为产物：
  描述：

  (9S)-dihydroerythronolide A 在 palladium dihydroxide camphor-10-sulfonic acid 、 氢气 、 4-甲基苯磺酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 75.5h， 生成 (9S)-9-dihydro-9,11-O-isopropylideneerythronolide A
  参考文献：
  名称：

  有效的2,6-脱水-2-硫代糖基糖基化在红霉素A全合成中的应用

  摘要：

  由（9S）-9-二氢赤藓醇内酯A（2）合成红霉素A（I），是通过2,6-脱水-2-硫代糖9的高度立体选择性和强力糖基化作为关键步骤而有效地实现的。

  DOI：

  10.1016/0040-4039(91)80777-4

文献信息

• Application of Highly Stereocontrolled Glycosidations Employing 2,6-Anhydro-2-thio Sugars to the Syntheses of Erythromycin A and Olivomycin A Trisaccharide
  作者：Kazunobu Toshima、Yuko Nozaki、Satsuki Mukaiyama、Tetsuro Tamai、Masaya Nakata、Kuniaki Tatsuta、Mitsuhiro Kinoshita

  DOI：10.1021/ja00118a008

  日期：1995.4

  The highly efficient syntheses of the erythromycin A (1) from its aglycon, (9S)-9-dihydroerythronolide A (4), and the C-D-E trisaccharide 3 of olivomycin A have been accomplished by the successful application of stereocontrolled glycosidations using 2,6-anhydro-2-thio sugars. The former synthesis includes the highly alpha-stereoselective glycosidation of the C5 desosaminated lactone 12 with phenyl 2,6-anhydro-4-O-benzyl-3-C-methyl-3-O-methyl-1 ,2-dithio-L-altropyranoside (10), which was achieved by using NIS-TfOH. The latter synthesis involves both the highly beta-stereoselective glycosidation of 1,3-di-O-acetyl-2,6-anhydro-4-O-benzyl-2-thio-beta-D-altropy (23), which was realized by employing TMSOTf, and the highly alpha-stereoselective glycosidation of phenyl 2,6-anhydro-3-O-(diethylisopropylsilyl) -4-O-isobutyryl-3-C-methyl-1,2-dithio-L-manno-pyranoside (24), which succeeded by utilizing NBS. Hydrogenolyses using Raney Ni as a catalyst and selective deprotections of the key glyco substances 17 and 22 led to the total syntheses of erythromycin A (1) and the C-D-E trisaccharide 3 of olivomycin A, respectively.