阿克拉菌酮 | 16234-96-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 并四苯
• 中文名称: 阿克拉菌酮
• 英文名称: aklavinone
• 英文别名: Aklavinon；methyl (1R,2R,4S)-2-ethyl-2,4,5,7-tetrahydroxy-6,11-dioxo-3,4-dihydro-1H-tetracene-1-carboxylate
• CAS: 16234-96-1
• 化学式: C₂₂H₂₀O₈
• 分子量: 412.396
• InChiKey: RACGRCLGVYXIAO-YOKWENHESA-N

物化性质

• 沸点：
  663.5±55.0 °C(Predicted)
• 密度：
  1.525±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  阿克拉菌酮 在 吡啶 、 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 、 三苯基膦氯金 、 pyridine hydrofluoride 、 双三氟甲烷磺酰亚胺银盐 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 7-[2-deoxy-α-L-fucopyranosyl-(1→4)-3-amino-2,3-dideoxy-α-L-fucopyranoside]-aklavinone
  参考文献：
  名称：

  Doxorubicin and Aclarubicin: Shuffling Anthracycline Glycans for Improved Anticancer Agents

  摘要：

  Anthracycline anticancer drugs doxorubicin and aclarubicin have been used in the clinic for several decades to treat various cancers. Although closely related structures, their molecular mode of action diverges, which is reflected in their biological activity profile. For a better understanding of the structure-function relationship of these drugs, we synthesized ten doxorubicin/aclarubicin hybrids varying in three distinct features: aglycon, glycan, and amine substitution pattern. We continued to evaluate their capacity to induce DNA breaks, histone eviction, and relocated topoisomerase II alpha in living cells. Furthermore, we assessed their cytotoxicity in various human tumor cell lines. Our findings underscore that histone eviction alone, rather than DNA breaks, contributes strongly to the overall cytotoxicity of anthracyclines, and structures containing N,N-dimethylamine at the reducing sugar prove that are more cytotoxic than their nonmethylated counterparts. This structural information will support further development of novel anthracycline variants with improved anticancer activity.

  DOI：

  10.1021/acs.jmedchem.0c01191
• 作为产物：
  描述：

  (10-Hydroxy-6,11-dioxo-6,11-dihydro-anthra[1,2-b]furan-4-yl)-acetic acid methyl ester 在 二甲基硫 、 4-甲基苯磺酸吡啶 、 四氯化锡 、 臭氧 作用下， 以 二氯甲烷 、 乙腈 、 苯 为溶剂， 反应 29.7h， 生成 阿克拉菌酮
  参考文献：
  名称：

  实用的aklavinone不对称合成

  摘要：

  以6a到10a的不对称醛醇缩合反应为关键步骤，实现了抗肿瘤抗生素Aclacinomycin A的糖苷配基（+）-aklavinone的实用合成。

  DOI：

  10.1016/s0040-4020(01)91530-3

文献信息

• [EN] NOVEL CHARTREUSIN ANALOGUES<br/>[FR] NOUVEAUX ANALOGUES DE CHARTREUSINE
  申请人：LEIBNIZ INST NATURSTOFF FORSCH

  公开号：WO2014019685A1

  公开（公告）日：2014-02-06

  The present invention relates to novel Chartreusin analogues of formula (I), pharmaceutical compositions comprising the same and to their use for the treatment of cancer and other diseases.

  本发明涉及公式（I）的新型查特鲁辛类似物，包括相同物质的药物组合物以及它们用于治疗癌症和其他疾病的用途。
• [EN] METHODS FOR THE SYNTHESIS OF AMRUBICIN<br/>[FR] PROCÉDÉS POUR LA SYNTHÈSE D'AMRUBICINE
  申请人：TBD BIODISCOVERY

  公开号：WO2010125466A1

  公开（公告）日：2010-11-04

  Methods for producing amrubicin and structural analogs thereof. The present invention encompasses synthetic pathways for the production of amrubicin (Formula I) and structural analogs thereof. The synthetic pathways of the present invention preferably employ as a starting material an anthracycline compound having the generic Formula (II): Compounds of Formula II may have any combination of the following identities for the indicated moieties: R1, R2, R3, R4, and R8 may be H, OH, or alkoxy; R5 may be H, alkyl, or alkoxycarbonyl; R6 may be H or alkyl; R7 may be OH or alkyl. In certain embodiments, ε-rhodomycinone or daunomycinone may be used as starting materials according to Formula (II). The present invention employs a compound of Formula (II) as part of a semi-synthetic method that combines traditional chemical synthetic steps with biosynthetic steps to produce amrubicin, derivatives thereof, and structural analogs thereof. The methods of the present invention preferably include a glycosylation reaction whereby an algycon of amrubicin or structural analog thereof is glycosylated to produce the final product.

  生产阿姆鲁比辛及其结构类似物的方法。本发明涵盖了用于生产阿姆鲁比辛（化学式I）及其结构类似物的合成途径。本发明的合成途径通常使用具有通用化学式（II）的蒽喜树碱化合物作为起始物质：化合物II的各个部分可能具有以下标识：R1、R2、R3、R4和R8可能是H、OH或烷氧基；R5可能是H、烷基或烷氧羰基；R6可能是H或烷基；R7可能是OH或烷基。在某些实施例中，ε-罗多霉素酮或多诺霉素酮可以按照化学式（II）作为起始材料。本发明采用化学式（II）的化合物作为半合成方法的一部分，将传统的化学合成步骤与生物合成步骤相结合，以生产阿姆鲁比辛、其衍生物和结构类似物。本发明的方法通常包括一种糖基化反应，通过该反应，阿姆鲁比辛的糖基化物或其结构类似物的糖基化物被合成为最终产物。
• Characterization of Rhodosaminyl Transfer by the AknS/AknT Glycosylation Complex and Its Use in Reconstituting the Biosynthetic Pathway of Aclacinomycin A
  作者：Catherine Leimkuhler、Micha Fridman、Tania Lupoli、Suzanne Walker、Christopher T. Walsh、Daniel Kahne

  DOI：10.1021/ja072909o

  日期：2007.8.1

  The tetracyclic core of anthracycline natural products with antitumor activity such as aclacinomycin A are tailored during biosynthesis by regioselective glycosylation. We report the first synthesis of TDP-L-rhodosamine and demonstrate that the glycosyltransferase AknS transfers L-rhodosamine to the aglycone to initiate construction of the side-chain trisaccharide. The partner protein AknT accelerates

  具有抗肿瘤活性的蒽环类天然产物（如阿克拉霉素 A）的四环核心在生物合成过程中通过区域选择性糖基化进行定制。我们报告了 TDP-L-罗多糖胺的首次合成，并证明糖基转移酶 AknS 将 L-罗多糖胺转移到苷元以启动侧链三糖的构建。伙伴蛋白 AknT 将用于 L-紫多糖胺转移的 AknS 周转率提高了 200 倍。AknT 不影响 Km，而是影响 kcat。使用这些数据，我们建议 AknT 导致 AknS 的构象变化，从而稳定过渡状态并最终增强转移。当随后的糖基转移酶 AknK 及其底物 TDP-L-岩藻糖也加入到苷元中时，
• New Betaclamycin and Aclarubicin Analogs Obtained by Prolonged Microbial Conversion with an Aclarubicin-negative Mutant.
  作者：OSAMU JOHDO、TAKEO YOSHIOKA、HIROSHI NAGANAWA、TOMIO TAKEUCHI、AKIHIRO YOSHIMOTO

  DOI：10.7164/antibiotics.49.669

  日期：——

  Microbial conversion of β-rhodomycinone and aklavinone using an aclarubicin-negative Streptomyces galilaeus mutant afforded new anthracycline antibiotics CG21-C and CG1-C which had a rednosyl-2-deoxyfucosyl-rhodosaminyl trisaccharide residue at C-7 of each added aglycone. They were produced only when a prolonged conversion culture took place. Because the usual conversion products containing a cinerulosyl-2-deoxyfucosyl-rhodosaminyl residue were at first accumulated and then decreased during further cultivation, it was evident that they occurred by the modification of terminal cinerulose. The isolation, purification, and structural determination are described, and cytotoxicity in vitro against cultured L1210 cells and the formation mechanism are discussed.

  使用一种阿克拉霉素阴性链霉菌（Streptomyces galilaeus）突变体对β-罗多霉素酮和阿克拉维酮进行微生物转化，获得了新的蒽环类抗生素CG21-C和CG1-C，它们在每个加合的糖苷的C-7处具有红苷-2-脱氧岩藻糖基-罗多霉素三糖残基。它们仅在长时间转化培养时产生。由于通常的转化产物含有红苷-2-脱氧岩藻糖基-罗多霉素残基，在进一步培养过程中首先积累然后减少，很明显它们是通过末端红苷的修饰而产生的。本文描述了分离、纯化和结构测定，并讨论了体外对培养的L1210细胞的细胞毒性和形成机制。
• New Anthracycline Antibiotics 10-epi-Oxaunomycin and 10-epi-11-Deoxyoxaunomycin.
  作者：OSAMU JOHDO、H. NISHIDA、R. OKAMOTO、AKIHIRO YOSHIMOTO、TOMIO TAKEUCHI

  DOI：10.7164/antibiotics.48.1153

  日期：——

  Two new anthracycline antibiotics, 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin, were photochemically obtained from anthracycline metabolites D788-1 (10-carboxy-13-deoxocarminomycin) and D788-3 (10-carboxy-ll-deoxy-13-deoxocarminomycin) and were examined for their growth inhibitory activities on cultured LI210 leukemic cells. Effects of the S configuration of C-10 and a hydroxyl group at C-11 on the bioactivity are discussed in comparison with oxaunomycin and 11-deoxyoxaunomycin.

  从蒽环类代谢物 D788-1（10-羧基-13-脱氧大环内酯霉素）和 D788-3（10-羧基-ll-脱氧-13-脱氧大环内酯霉素）光化学方法获得了两种新的蒽环类抗生素--10-表-氧杂霉素和 10-表-11-脱氧氧杂霉素，并考察了它们对培养的 LI210 白血病细胞的生长抑制活性。通过与奥沙霉素和 11-脱氧奥沙霉素进行比较，讨论了 C-10 的 S 构型和 C-11 的羟基对生物活性的影响。