pseudomycin C' | 162443-73-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: pseudomycin C'
• 英文别名: (2S)-2-[(3S,6S,9Z,12S,15S,18S,21S,24R,27S)-18-(4-aminobutyl)-15,24-bis(2-aminoethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-ethylidene-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxyhexadecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octazacyclooctacos-6-yl]-2-hydroxyacetic acid
• CAS: 162443-73-4
• 化学式: C₅₃H₉₁ClN₁₂O₁₉
• 分子量: 1235.83
• InChiKey: KZSKIDBMTSZKLE-KIFSZDOYSA-N

物化性质

• 沸点：
  1634.425±65.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.366±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  85
• 可旋转键数：
  30
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  522
• 氢给体数：
  18
• 氢受体数：
  22

反应信息

• 作为反应物：
  描述：

  pseudomycin C' 、 ((((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)oxy)methyl pivalate 以40%的产率得到
  参考文献：
  名称：

  N -Acyloxymethyl carbamate linked prodrugs of pseudomycins are novel antifungal agents

  摘要：

  We describe herein the synthesis, bioconversion, antifungal activity, and preliminary toxicology evaluation of a series of N-acyloxymethyl carbamate linked triprodrugs of pseudomycins. The syntheses of these prodrugs (3-6) were achieved via simple N-acylation of PSB (1) or PSC ' (2) with various prodrug linkers (7-9). As expected, upon incubation with mouse and/or human plasma, many of these prodrugs (3, 5, and 6) were converted to the parent compound within a few hours. Of particular significance, two pseudomycin triprodrugs (5 and 6) showed excellent in vivo efficacy against systemic Candidiasis without tail vein irritation being observed. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00333-x
• 作为产物：
  描述：

  在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以65%的产率得到pseudomycin C'
  参考文献：
  名称：

  The synthesis of pseudomycin C′ via a novel acid promoted side-chain deacylation of pseudomycin A

  摘要：

  The gamma hydroxyl present in the aliphatic side chain of the natural products pseudomycin A and C' provided a unique handle for the pH dependent side-chain deacylation. Low pH reaction conditions were used to cleave the side chain with minimal degradation of the peptide core. The pseudomycin nucleus intermediate obtained from the deacylation of pseudomycin A was pivotal in the synthesis of novel side-chain analogues. A practical synthesis of a minor fermentation factor pseudomycin C' and related analogues is reported. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00613-2

文献信息

• Synthesis and Evaluation of Oxodioxolenylmethyl Carbamate Prodrugs of Pseudomycins
  作者：Xicheng Sun、Michael Rodriguez、Doug Zeckner、Bobbie Sachs、William Current、Robert Boyer、Jonathan Paschal、Carl McMillian、Shu-Hui Chen

  DOI：10.1021/jm000425w

  日期：2001.8.1

  With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C ' 3. It is rather encouraging to note that several members of the newly synthesized prodrugs described herein (e.g., 2a, 2e, and 4e) exhibited comparable in vivo efficacy to that achieved by the parent compounds, yet free of tail vein irritation and histamine induced toxicity in vivo.
• The synthesis of pseudomycin C′ via a novel acid promoted side-chain deacylation of pseudomycin A
  作者：Michael J Rodriguez、Matthew Belvo、Robert Morris、Douglas J Zeckner、William L Current、Roberta K Sachs、Mark J Zweifel

  DOI：10.1016/s0960-894x(00)00613-2

  日期：2001.1

  The gamma hydroxyl present in the aliphatic side chain of the natural products pseudomycin A and C' provided a unique handle for the pH dependent side-chain deacylation. Low pH reaction conditions were used to cleave the side chain with minimal degradation of the peptide core. The pseudomycin nucleus intermediate obtained from the deacylation of pseudomycin A was pivotal in the synthesis of novel side-chain analogues. A practical synthesis of a minor fermentation factor pseudomycin C' and related analogues is reported. (C) 2001 Elsevier Science Ltd. All rights reserved.
• N -Acyloxymethyl carbamate linked prodrugs of pseudomycins are novel antifungal agents
  作者：Xicheng Sun、Douglas J Zeckner、William L Current、Robert Boyer、Carl McMillian、Nathan Yumibe、Shu-Hui Chen

  DOI：10.1016/s0960-894x(01)00333-x

  日期：2001.7

  We describe herein the synthesis, bioconversion, antifungal activity, and preliminary toxicology evaluation of a series of N-acyloxymethyl carbamate linked triprodrugs of pseudomycins. The syntheses of these prodrugs (3-6) were achieved via simple N-acylation of PSB (1) or PSC ' (2) with various prodrug linkers (7-9). As expected, upon incubation with mouse and/or human plasma, many of these prodrugs (3, 5, and 6) were converted to the parent compound within a few hours. Of particular significance, two pseudomycin triprodrugs (5 and 6) showed excellent in vivo efficacy against systemic Candidiasis without tail vein irritation being observed. (C) 2001 Elsevier Science Ltd. All rights reserved.