(2R,3S,4S)-4-(dibenzylamino)-3-hydroxy-2-methyl-5-(pyridin-3-yl)pentanoic acid | 1416772-46-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: (2R,3S,4S)-4-(dibenzylamino)-3-hydroxy-2-methyl-5-(pyridin-3-yl)pentanoic acid
• 英文别名: (2R,3S,4S)-4-(dibenzylamino)-3-hydroxy-2-methyl-5-pyridin-3-ylpentanoic acid
• CAS: 1416772-46-7
• 化学式: C₂₅H₂₈N₂O₃
• 分子量: 404.509
• InChiKey: QTPWHORWMHJZJW-YGOYIFOWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  73.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S)-4-(dibenzylamino)-3-hydroxy-2-methyl-5-(pyridin-3-yl)pentanoic acid 在 2,4,6-三氯苯甲酰氯 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， -78.0~20.0 ℃ 、100.0 kPa 条件下， 反应 45.08h， 生成
  参考文献：
  名称：

  C2修饰的抗分枝杆菌天然产物吡咯霉素类似物的合成和构效关系研究。

  摘要：

  已经制备了一系列抗分枝杆菌天然产物吡咯霉素的衍生物，其中C2侧链通过CC单键连接到大环核心结构上，代替了天然产物中合成上要求更高的烯醇酯双键。足够大小的疏水性C2取代基通常为这些二氢吡啶霉素提供强大的抗Mtb活性（最小抑制浓度（MIC）约为2.5μM），因此一些类似物接近天然吡咯霉素的活性。令人惊奇地，与吡啶霉素相反，这些化合物中的一些对结核分枝杆菌（Mtb）中InhA的过表达不敏感。

  DOI：

  10.1021/acs.jmedchem.9b01457
• 作为产物：
  描述：

  N-acetyl-(β-3-pyridyl)-α,β-dehydroalanine 在 chromium dichloride 、 sodium chlorite 、 sodium periodate 、 sodium dihydrogenphosphate 、 lithium aluminium tetrahydride 、 tetrafluoroboric acid 、 氯化亚砜 、 2,3-二甲基-2-丁烯 、 (R,R)-(-)-1,2-bis[(o-methoxyphenyl)(phenyl) phosphino]ethane(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate 、 甲基磺酰胺 、 AD-mix-α 、 氢气 、 sodium acetate 、 sodium cyanoborohydride 、 戴斯-马丁氧化剂 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 200.0 ℃ 、500.01 kPa 条件下， 反应 211.17h， 生成 (2R,3S,4S)-4-(dibenzylamino)-3-hydroxy-2-methyl-5-(pyridin-3-yl)pentanoic acid
  参考文献：
  名称：

  Synthesis and Antimycobacterial Activity of 2,1′-Dihydropyridomycins

  摘要：

  Dihydropyridomycins 2 and 3, which lack the characteristic enol ester moiety of the potent antimycobacterial natural product pyridomycin (1), have been prepared from L-Thr, R- and S-hydroxy isovaleric acid, and 3-pyridinecarboxaldehyde. The 2R isomer 2 shows only 4-fold lower anti-Mtb activity than 1, indicating that the enol ester moiety in the natural product is not critical for its biological activity. This finding establishes 2 as a potent and more practical lead for anti-TB drug discovery.

  DOI：

  10.1021/ml300385q

文献信息

• PYRIDOMYCIN BASED COMPOUNDS EXHIBITING AN ANTITUBERCULAR ACTIVITY
  申请人：ETH Zurich

  公开号：US20150246907A1

  公开（公告）日：2015-09-03

  Formula (1), X 1 represents O or NR 6 , X 2 represents O or NR 6 , X 3 represents O or NR 1 , R 1 represents H or C 1 to C 3 alkyl, R 2 represents H, or linear or branched C 1 -C 8 alkyl optionally including one or more heteroatoms, cyclopropyl, cyclobutyl, cyclohexyl or oxetanyl or amino acid side chain or protected amino acid side chain, or R 1 and R 2 may form together a saturated, partly saturated or unsaturated 5 or 6 membered ring system, optionally substituted, R 3 represents H, cyclopentyl, cyclohexyl, aryl or hydroxyaryl, aryl or hydroxyaryl being optionally substituted by fluorine, or linear or branched C 1 to C 8 alkyl optionally including a hetero atom, R 4 represents phenyl or 5- or 6-membered heterocycles including one or more nitrogen or oxygen atoms optionally substituted with 1 to 4, respectively 5 fluorine atoms, and R 6 represents H, or linear or branched alkyl chain having 1 to 3 carbon atoms.

  公式（1），X1代表O或NR6，X2代表O或NR6，X3代表O或NR1，R1代表H或C1到C3烷基，R2代表H，或线性或支链的C1-C8烷基，可选地包括一个或多个杂原子，环丙基，环丁基，环己基或氧环丙基或氨基酸侧链或保护的氨基酸侧链，或R1和R2可以形成一个饱和的，部分饱和的或不饱和的5或6成员环系统，可选地取代，R3代表H，环戊基，环己基，芳基或羟基芳基，芳基或羟基芳基可选地被氟取代，或线性或支链的C1到C8烷基，可选地包括一个杂原子，R4代表苯或包括一个或多个氮或氧原子的5-或6成员杂环，可选地用1到4，分别用5氟原子取代，R6代表H，或具有1到3个碳原子的线性或支链烷基链。
• [EN] PYRIDOMYCIN BASED COMPOUNDS EXHIBITING AN ANTITUBERCULAR ACTIVITY<br/>[FR] COMPOSÉS À BASE DE PYRIDOMYCINE AYANT UNE ACTIVITÉ ANTITUBERCULEUSE
  申请人：ETH ZUERICH

  公开号：WO2014040709A1

  公开（公告）日：2014-03-20

  The present invention relates to a compound of formula (1) wherein X1 represents O or NR6, X2 represents O or NR6, X3 represents O or NR1, R1 represents H or C1 to C3 alkyl, R2 represents H, or a linear or branched C1 - C8 alkyl optionally comprising one or more heteroatoms, cyclopropyl, cyclobutyl, cyclohexyl or oxetanyl or an amino acid side chain or a protected amino acid side chain, or R1 and R2 may form together a 5 or 6 membered ring system which may be saturated, partly saturated or unsaturated, said ring system being optionally substituted, R3 represents H, cyclopentyl, cyclohexyl, aryl or hydroxyaryl, said aryl or hydroxyaryl being optionally substituted by fluorine, or linear or branched C1 to C8 alkyl optionally comprising a hetero atom, R4 represents phenyl or 5- or 6-membered heterocycles comprising one or more nitrogen or oxygen atoms optionally substituted with 1 to 4, respectively 5 fluorine atoms, and R6 represents H, or a linear or branched alkyl chain having 1 to 3 carbon atoms their use as a medicament for the treatment of bacterial infections, in particular for treatment of tuberculosis.
• Synthesis and Structure–Activity Relationship Studies of C2-Modified Analogs of the Antimycobacterial Natural Product Pyridomycin
  作者：Maryline Kienle、Patrick Eisenring、Barbara Stoessel、Oliver P. Horlacher、Samuel Hasler、Gwénaëlle van Colen、Ruben C. Hartkoorn、Anthony Vocat、Stewart T. Cole、Karl-Heinz Altmann

  DOI：10.1021/acs.jmedchem.9b01457

  日期：2020.2.13

  A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond found in the natural product. Hydrophobic C2 substituents of sufficient size generally provide for potent anti-Mtb activity of these dihydropyridomycins

  已经制备了一系列抗分枝杆菌天然产物吡咯霉素的衍生物，其中C2侧链通过CC单键连接到大环核心结构上，代替了天然产物中合成上要求更高的烯醇酯双键。足够大小的疏水性C2取代基通常为这些二氢吡啶霉素提供强大的抗Mtb活性（最小抑制浓度（MIC）约为2.5μM），因此一些类似物接近天然吡咯霉素的活性。令人惊奇地，与吡啶霉素相反，这些化合物中的一些对结核分枝杆菌（Mtb）中InhA的过表达不敏感。
• Synthesis and Antimycobacterial Activity of 2,1′-Dihydropyridomycins
  作者：Oliver P. Horlacher、Ruben C. Hartkoorn、Stewart T. Cole、Karl-Heinz Altmann

  DOI：10.1021/ml300385q

  日期：2013.2.14

  Dihydropyridomycins 2 and 3, which lack the characteristic enol ester moiety of the potent antimycobacterial natural product pyridomycin (1), have been prepared from L-Thr, R- and S-hydroxy isovaleric acid, and 3-pyridinecarboxaldehyde. The 2R isomer 2 shows only 4-fold lower anti-Mtb activity than 1, indicating that the enol ester moiety in the natural product is not critical for its biological activity. This finding establishes 2 as a potent and more practical lead for anti-TB drug discovery.