N-乙酰-凯立霉素 | 108212-76-6

• 物质功能分类: 原料药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: N-乙酰-凯立霉素
• 英文名称: N-acetyl calicheamicin
• 英文别名: N-acetyl calicheamicin γ 1；N-Acetyl-Calicheamicin；S-[(2R,3S,4S,6S)-6-[[(2R,3S,4S,5R,6R)-5-[(2S,4S,5S)-5-[acetyl(ethyl)amino]-4-methoxyoxan-2-yl]oxy-4-hydroxy-6-[[(2S,5Z,9R,13E)-9-hydroxy-12-(methoxycarbonylamino)-13-[2-(methyltrisulfanyl)ethylidene]-11-oxo-2-bicyclo[7.3.1]trideca-1(12),5-dien-3,7-diynyl]oxy]-2-methyloxan-3-yl]amino]oxy-4-hydroxy-2-methyloxan-3-yl] 4-[(2S,3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyloxan-2-yl]oxy-5-iodo-2,3-dimethoxy-6-methylbenzenecarbothioate
• CAS: 108212-76-6
• 化学式: C₅₇H₇₆IN₃O₂₂S₄
• 分子量: 1410.41
• InChiKey: WPDOZYZAJKUVRZ-IOCYQWGVSA-N

物化性质

• 密度：
  1.56±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  87
• 可旋转键数：
  24
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  418
• 氢给体数：
  7
• 氢受体数：
  27

制备方法与用途

生物活性

N-Acetyl-Calicheamicin是一类高活性抗肿瘤的抗生素。

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 N-乙酰-凯立霉素 在 4-二甲氨基吡啶 作用下， 生成
  参考文献：
  名称：

  Calicheamicins, a novel family of antitumor antibiotics. 4. Structure elucidation of calicheamicins .beta.1Br, .gamma.1Br, .alpha.2I, .alpha.3I, .beta.1I, .gamma.1I, and .delta.1I

  摘要：

  The details of the structural assignment of the potent antitumor antibiotic, calicheamicin gamma-1I (6, C55H74IN3O21S4), is reported. Methanolysis studies on 6 and N-acetylcalicheamicin gamma-1I (8, C57H76IN3022S4) permitted the structural assignment of the glycosidic chain. Details of the spectral analysis supporting the assignments of the 3-O-methyl-alpha-L-rhamnopyranoside (D-ring) and the methyl 2,4-dideoxy-3-O-methyl-4-(N-acetyl-N-ethylamino)-a-L-xylopyranoside (E-ring) is reported. The structure of calicheamicinone (32, C18H17NO5S3), containing a bicyclo[7.3.1 ] tridec-9-ene-2,6-diyne system and a methyl trisulfide, was elucidated by a series of chemical degradation studies, which included an unexpected free radical cycloaromatization reaction. The presence of 4,6-dideoxy-4-(hydroxyamino)-beta-D-glucopyranoside (A-ring) and its N-O glycosidic linkage to the thio sugar (B-ring) was ascertained by X-ray crystallography of 24 (C36H40INO13S2), a degradation product of 6. The chemical structures of calicheamicins beta-1Br (1), gamma-1Br (2), alpha-2I (3), alpha-3I (4), beta-1I (5), and delta-1I (7) were assigned by correlating their H-1 and C-13 NMR data with that of calicheamicin gamma-1I. By tracking the biological activities of the degradation products, the enediyne system of calicheamicinone was shown to be essential for the DNA-damaging abilities of the calicheamicins. A mechanism whereby the enediyne could be triggered to cyclize via a 1,4-diyl, the putative DNA cleaving species, is proposed.

  DOI：

  10.1021/ja00029a030
• 作为产物：
  描述：

  乙酸酐 、 卡利奇霉素 以 甲醇 为溶剂， 反应 4.0h， 生成 N-乙酰-凯立霉素
  参考文献：
  名称：

  Calicheamicins, a novel family of antitumor antibiotics. 4. Structure elucidation of calicheamicins .beta.1Br, .gamma.1Br, .alpha.2I, .alpha.3I, .beta.1I, .gamma.1I, and .delta.1I

  摘要：

  The details of the structural assignment of the potent antitumor antibiotic, calicheamicin gamma-1I (6, C55H74IN3O21S4), is reported. Methanolysis studies on 6 and N-acetylcalicheamicin gamma-1I (8, C57H76IN3022S4) permitted the structural assignment of the glycosidic chain. Details of the spectral analysis supporting the assignments of the 3-O-methyl-alpha-L-rhamnopyranoside (D-ring) and the methyl 2,4-dideoxy-3-O-methyl-4-(N-acetyl-N-ethylamino)-a-L-xylopyranoside (E-ring) is reported. The structure of calicheamicinone (32, C18H17NO5S3), containing a bicyclo[7.3.1 ] tridec-9-ene-2,6-diyne system and a methyl trisulfide, was elucidated by a series of chemical degradation studies, which included an unexpected free radical cycloaromatization reaction. The presence of 4,6-dideoxy-4-(hydroxyamino)-beta-D-glucopyranoside (A-ring) and its N-O glycosidic linkage to the thio sugar (B-ring) was ascertained by X-ray crystallography of 24 (C36H40INO13S2), a degradation product of 6. The chemical structures of calicheamicins beta-1Br (1), gamma-1Br (2), alpha-2I (3), alpha-3I (4), beta-1I (5), and delta-1I (7) were assigned by correlating their H-1 and C-13 NMR data with that of calicheamicin gamma-1I. By tracking the biological activities of the degradation products, the enediyne system of calicheamicinone was shown to be essential for the DNA-damaging abilities of the calicheamicins. A mechanism whereby the enediyne could be triggered to cyclize via a 1,4-diyl, the putative DNA cleaving species, is proposed.

  DOI：

  10.1021/ja00029a030

文献信息

• [EN] INTERMEDIATES AND METHODS FOR SYNTHESIZING CALICHEAMICIN DERIVATIVES<br/>[FR] INTERMÉDIAIRES ET PROCÉDÉS DE SYNTHÈSE DE DÉRIVÉS DE LA CALICHÉAMICINE
  申请人：PFIZER

  公开号：WO2015063680A1

  公开（公告）日：2015-05-07

  The present invention relates to intermediates of Formula (I) and to methods of synthesizing and purifying calicheamicin derivatives.

  本发明涉及式(I)的中间体以及合成和纯化卡利奇阿霉素衍生物的方法。
• [EN] ANTI-SEZ6 ANTIBODY DRUG CONJUGATES AND METHODS OF USE<br/>[FR] CONJUGUÉS ANTICORPS ANTI-SEZ6-MÉDICAMENTS ET PROCÉDÉS D'UTILISATION
  申请人：ABBVIE STEMCENTRX LLC

  公开号：WO2019232241A1

  公开（公告）日：2019-12-05

  Provided are novel anti-SEZ6 antibodies and antibody drug conjugates, and methods of using such anti-SEZ6 antibodies and antibody drug conjugates to treat cancer.

  提供了新型抗SEZ6抗体和抗体药物偶联物，以及使用这些抗SEZ6抗体和抗体药物偶联物治疗癌症的方法。