autolytimycin | 299173-64-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: autolytimycin
• 英文别名: EH21A2；KOS-1806；progeldanamycin；[(4E,8S,9S,10E,12S,13R,14S,16R)-13,20-dihydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-9-yl] carbamate
• CAS: 299173-64-1
• 化学式: C₂₈H₄₂N₂O₇
• 分子量: 518.651
• InChiKey: HUXWGTSMSXMDBH-UQMARRQJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (4E,8S,9S,10E,12S,13R,14S,16R)-carbamic acid 20-(benzyloxy)-8,14-dimethoxy-13-(methoxymethoxy)-4,10,12,16-tetramethyl-3-oxo-2-aza-bicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-9-yl ester 在 aluminum (III) chloride 、 苯甲醚 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 以76%的产率得到autolytimycin
  参考文献：
  名称：

  Synthesis of Reblastatin, Autolytimycin, and Non-Benzoquinone Analogues: Potent Inhibitors of Heat Shock Protein 90

  摘要：

  A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (similar to 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (similar to 100 nM).

  DOI：

  10.1021/jo1000109

文献信息

• Macrolactams by engineered biosynthesis
  申请人：Ashley Gary W.

  公开号：US20080188450A1

  公开（公告）日：2008-08-07

  Macrolactams are made by feeding aromatic amino acids as replacement starter units to a mutant strain of the geldanamycin-producing microorganism Streptomyces hygroscopicus var. geldanus NRRL 3602, wherein the gene cluster encoding enzymes for the biosynthesis of the natural starter unit 3-amino-5-hydroxybenzoic acid has been deleted.

  大环内酰胺是通过将芳香族氨基酸作为替代起始单元供应给生产格尔达霉素的微生物链霉菌属湿生链霉菌格尔达努斯NRRL 3602的突变菌株制备的，其中编码天然起始单元3-氨基-5-羟基苯甲酸生物合成酶的基因簇已被删除。
• 18 ,21-Didesoxymacbecin Derivatives for the Treatment of Cancer
  申请人：Martin Christine

  公开号：US20090253667A1

  公开（公告）日：2009-10-08

  The present invention relates to 18,21-didesoxymacbecin analogues that are useful, e.g. in the treatment of cancer, B-cell malignancies, malaria, fungal infection, diseases of the central nervous system and neurodegenerative diseases, diseases dependent on angiogenesis, autoimmune diseases and/or as a prophylactic pre-treatment for cancer. The present invention also provides methods for the production of these compounds and their use in medicine, in particular in the treatment and/or prophylaxis of cancer or B-cell malignancies.
• US7855192B2
  申请人：——

  公开号：US7855192B2

  公开（公告）日：2010-12-21
• US8492370B2
  申请人：——

  公开号：US8492370B2

  公开（公告）日：2013-07-23
• [EN] MACROLACTAMS BY ENGINEERED BIOSYNTHESIS<br/>[FR] MACROLACTAMES OBTENUS PAR BIOSYNTHÈSE MODIFIÉE
  申请人：KOSAN BIOSCIENCES INC

  公开号：WO2008094438A1

  公开（公告）日：2008-08-07

  [EN] Macrolactams are made by feeding aromatic amino acids as replacement starter units to a mutant strain of the geldanamycin-producing microorganism Streptomyces hygroscopicus var. geldanus NRRL 3602, wherein the gene cluster encoding enzymes for the biosynthesis of the natural starter unit 3-amino-5-hydroxybenzoic acid has been deleted.
  [FR] Selon la présente invention, les macrolactames sont préparés en alimentant une souche mutante du microorganisme produisant de la geldanamycine Streptomyces hygroscopicus var. geldanus NRRL 3602 en acides aminés aromatiques en tant qu'unités de départ de substitution, souche dans laquelle le groupe de gènes qui code pour les enzymes de biosynthèse de l'unité de départ naturelle, l'acide 3-amino-5-hydroxybenzoïque, a été délété.