(18R,21R,24R,27R,30S)-18-amino-21,27-bis(3,5-dichloro-4-hydroxyphenyl)-37-hydroxy-29-methyl-19,22,25,28-tetraoxo-2-oxa-14,20,23,26,29-pentazahexacyclo[30.2.2.13,7.05,24.08,13.012,16]heptatriaconta-1(34),3,5,7(37),8,10,12,15,32,35-decaene-30-carboxylic acid

• 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: (18R,21R,24R,27R,30S)-18-amino-21,27-bis(3,5-dichloro-4-hydroxyphenyl)-37-hydroxy-29-methyl-19,22,25,28-tetraoxo-2-oxa-14,20,23,26,29-pentazahexacyclo[30.2.2.13,7.05,24.08,13.012,16]heptatriaconta-1(34),3,5,7(37),8,10,12,15,32,35-decaene-30-carboxylic acid
• 化学式: C₄₅H₃₆Cl₄N₆O₁₀
• 分子量: 962.627
• InChiKey: ITEJDHVEYLBYQP-DDFLMXQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  65
• 可旋转键数：
  3
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  257
• 氢给体数：
  9
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  chloropeptin I 在 盐酸 、 溶剂黄146 、 巯基乙酸 作用下， 反应 4.0h， 生成 (18R,21R,24R,27R,30S)-18-amino-21,27-bis(3,5-dichloro-4-hydroxyphenyl)-37-hydroxy-29-methyl-19,22,25,28-tetraoxo-2-oxa-14,20,23,26,29-pentazahexacyclo[30.2.2.13,7.05,24.08,13.012,16]heptatriaconta-1(34),3,5,7(37),8,10,12,15,32,35-decaene-30-carboxylic acid
  参考文献：
  名称：

  Selective and controlled hydrolysis of chloropeptin I. HIV-1 integrase activity of fragments

  摘要：

  Selective amide bond cleavages of chloropeptin I were accomplished using trifluoroacetic acid (TFA), and a mixture of acetic acid, hydrochloric acid and thioglycolic acid. The hydrolysis products maintaining the bicyclic core retained HIV-1 integrase inhibitory activity similar to that of the chloropeptin I. The hydrolysis products and their HIV-1 integrase activities are described. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)01993-5

文献信息

• The Complestatins as HIV-1 Integrase Inhibitors. Efficient Isolation, Structure Elucidation, and Inhibitory Activities of Isocomplestatin, Chloropeptin I, New Complestatins, A and B, and Acid-Hydrolysis Products of Chloropeptin I
  作者：Sheo B. Singh、Hiranthi Jayasuriya、Gino M. Salituro、Deborah L. Zink、Ali Shafiee、Brian Heimbuch、Keith C. Silverman、Russell B. Lingham、Olga Genilloud、Ana Teran、Dolores Vilella、Peter Felock、Daria Hazuda

  DOI：10.1021/np000632z

  日期：2001.7.1

  microM), and HIV-1 replication (200 nM) in virus-infected cells. Attempted large-scale isolation of 1 by the literature method, used for the isolation of complestatin, led to lower yield and limited availability. We have developed several new, two-step, high-yielding absorption/elution methods of isolation based on reverse-phase chromatography at pH 8 that are applicable to scales from one gram to potential

  通过筛选微生物提取物文库，异complestatin（1）（一种已知的刚性双环六肽）complestatin（2）的新轴向手性异构体被鉴定为有效的天然产物HIV-1整合酶（一种独特的酶）抑制剂负责病毒复制。异complestatin在病毒感染的细胞中，在偶联的3'-末端加工/链转移（200 nM），链转移（4 microM）和HIV-1复制（200 nM）中显示抑制活性（IC（50））。尝试通过文献方法大规模分离1用于分离补全他汀，导致产量降低和可用性有限。我们已经开发了几种新的，两步的，高分离度的吸收/洗脱方法，基于pH 8的反相色谱法，适用于从1克到潜在工业规模的规模。我们还发现并确定了两个新的同源物1的结构，即complestatins A（4）和B（5），它们具有几乎相等的HIV-1整合酶活性。它们在色氨酸部分的C2'和C3'（残基F）处不同于1。氯肽素I（3）的选择性酸水解，其本