9-[(acetoxy)methyl]-6,7,9,14,14a,15-hexahydro-7-hydroxy-2,11-dimethoxy-3,12,16-trimethyl-(6S,7S,9R,14aS,15R)-(-)-6,15-imino-4H-isoquino[3,2-b][3]benzazocine-1,4,10,13(5H)-tetrone | 304852-37-7

分子结构分类

有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物

中文名称

——

中文别名

——

英文名称

9-[(acetoxy)methyl]-6,7,9,14,14a,15-hexahydro-7-hydroxy-2,11-dimethoxy-3,12,16-trimethyl-(6S,7S,9R,14aS,15R)-(-)-6,15-imino-4H-isoquino[3,2-b][3]benzazocine-1,4,10,13(5H)-tetrone

英文别名

(-)-jorumycin；jorumycin；[(1R,2S,10R,12S,13S)-12-hydroxy-7,18-dimethoxy-6,17,21-trimethyl-5,8,16,19-tetraoxo-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),6,15(20),17-tetraen-10-yl]methyl acetate

9-[(acetoxy)methyl]-6,7,9,14,14a,15-hexahydro-7-hydroxy-2,11-dimethoxy-3,12,16-trimethyl-(6S,7S,9R,14aS,15R)-(-)-6,15-imino-4H-isoquino[3,2-b][3]benzazocine-1,4,10,13(5H)-tetrone化学式

CAS

304852-37-7

化学式

C₂₇H₃₀N₂O₉

mdl

——

分子量

526.543

InChiKey

QCUVHQFXYHRYHX-PIHYCAAOSA-N

BEILSTEIN

——

EINECS

——

物化性质

沸点：

735.3±60.0 °C(Predicted)
密度：

1.44±0.1 g/cm3(Predicted)

计算性质

辛醇/水分配系数(LogP)：

0.1
重原子数：

38
可旋转键数：

5
环数：

5.0
sp3杂化的碳原子比例：

0.52
拓扑面积：

140
氢给体数：

1
氢受体数：

11

上下游信息

上游原料

中文名称	英文名称	CAS号	化学式	分子量
——	9-(acetoxymethyl)-7-cyano-6,7,9,14,14a,15-hexahydro-2,11-dimethoxy-3,12,16-trimethyl-(6S,7R,9R,14aS,15R)-(-)-6,15-imino-4H-isoquino[3,2-b][3]benzazocine-1,4,10,13(5H)-tetrone	701911-94-6	C₂₈H₂₉N₃O₈	535.554
——	renieramycin M	631913-64-9	C₃₁H₃₃N₃O₈	575.618
——	jorunnamycin A	701911-92-4	C₂₆H₂₇N₃O₇	493.516
N-{[(1S,2S,10R,12S,13S)-12,18-二羟基-7,17-二甲氧基-6,16,21-三甲基-5,8-二氧代-11,21-二氮杂五环[11.7.1.02,11.04,9.015,20]二十一-4(9),6,15,17,19-五烯-10-基]甲基}-L-丙氨酰胺	safracin B	87578-99-2	C₂₈H₃₆N₄O₇	540.616
——	(2S)-N-[[(1R,2S,10R,12R,13S)-12-cyano-19-hydroxy-7,18-dimethoxy-6,17,21-trimethyl-5,8-dioxo-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),6,15(20),16,18-pentaen-10-yl]methyl]-2-(phenylcarbamothioylamino)propanamide	308359-16-2	C₃₆H₄₀N₆O₆S	684.816
——	9H-fluoren-9-ylmethyl N-[(2S)-3-[5-[tert-butyl(dimethyl)silyl]oxy-2,4-dimethoxy-3-methylphenyl]-1-[(1R,3S)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-5,7-dimethoxy-6-methyl-8-prop-2-enoxy-1-(prop-2-enoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-oxopropan-2-yl]carbamate	866110-76-1	C₅₉H₈₂N₂O₁₁Si₂	1051.48
——	tert-butyl (1R,3S,6R,11aS)-1-hydroxy-3-[(5-hydroxy-2,4-dimethoxy-3-methylphenyl)methyl]-8,10-dimethoxy-9-methyl-4-oxo-7-prop-2-enoxy-6-(prop-2-enoxymethyl)-3,6,11,11a-tetrahydro-1H-pyrazino[1,2-b]isoquinoline-2-carboxylate	866110-78-3	C₃₇H₅₀N₂O₁₁	698.811
——	tert-butyl N-[(2S)-3-[5-[tert-butyl(dimethyl)silyl]oxy-2,4-dimethoxy-3-methylphenyl]-1-[(1R,3S)-3-(hydroxymethyl)-5,7-dimethoxy-6-methyl-8-prop-2-enoxy-1-(prop-2-enoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-oxopropan-2-yl]carbamate	866110-77-2	C₄₃H₆₆N₂O₁₁Si	815.089
——	(1R,2S,10R,13S)-19-hydroxy-5,7,16,18-tetramethoxy-6,17,21-trimethyl-8-prop-2-enoxy-10-(prop-2-enoxymethyl)-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),5,7,15(20),16,18-hexaen-12-one	866110-79-4	C₃₃H₄₂N₂O₈	594.705
——	(1R,2S,10R,13S)-19-hydroxy-5,7,16,18-tetramethoxy-6,17-dimethyl-8-prop-2-enoxy-10-(prop-2-enoxymethyl)-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),5,7,15(20),16,18-hexaen-12-one	866110-90-9	C₃₂H₄₀N₂O₈	580.678
——	bishydroquinonerenieramycin M	701911-93-5	C₃₁H₃₇N₃O₈	579.65
——	(1R,2S,10R,13S)-8,19-dihydroxy-10-(hydroxymethyl)-7,18-dimethoxy-6,17,21-trimethyl-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),5,7,15(20),16,18-hexaen-12-one	1177255-45-6	C₂₅H₃₀N₂O₆	454.523

反应信息

作为反应物：

描述：

9-[(acetoxy)methyl]-6,7,9,14,14a,15-hexahydro-7-hydroxy-2,11-dimethoxy-3,12,16-trimethyl-(6S,7S,9R,14aS,15R)-(-)-6,15-imino-4H-isoquino[3,2-b][3]benzazocine-1,4,10,13(5H)-tetrone 在 selenium(IV) oxide 、对甲苯磺酸作用下，以 1,4-二氧六环为溶剂，反应 12.0h，以37.2%的产率得到(7-methoxy-6-methyl-5,8-dioxo-5,8-didydro-1-isoquinolyl)methyl acetate

参考文献：

名称：

Chemistry of renieramycins. Part 6: Transformation of renieramycin M into jorumycin and renieramycin J including oxidative degradation products, mimosamycin, renierone, and renierol acetate

摘要：

The transformation of remeramycin M (1m) into renieramycin J (1j) and jorumycin (2) is presented along with the results of antiproliferative assay data. The chemical stability and the oxidative degradation of 2 and renieramycm E (1e) to generate simple isoquinoline alkaloids, such as mimosamycin (7), renierol acetate (12), and renierone (8) are also described. (C) 2004 Elsevier Ltd. All rights reserved.

DOI：

10.1016/j.tet.2004.02.071
作为产物：

描述：

(1R,2S,10R,13S)-19-hydroxy-5,7,16,18-tetramethoxy-6,17,21-trimethyl-8-prop-2-enoxy-10-(prop-2-enoxymethyl)-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),5,7,15(20),16,18-hexaen-12-one 在吡啶、 lithium aluminium tetrahydride 、 silver nitrate 、 2,3-二氯-5,6-二氰基-1,4-苯醌作用下，以四氢呋喃、丙酮、乙腈为溶剂，反应 32.5h，生成 9-[(acetoxy)methyl]-6,7,9,14,14a,15-hexahydro-7-hydroxy-2,11-dimethoxy-3,12,16-trimethyl-(6S,7S,9R,14aS,15R)-(-)-6,15-imino-4H-isoquino[3,2-b][3]benzazocine-1,4,10,13(5H)-tetrone

参考文献：

名称：

(-)-Jorumycin、(-)-Renieramycin G、3-epi-Jorumycin 和 3-epi-Renieramycin G 的不对称全合成

摘要：

(-)-jorumycin (1) 和 (-)-renieramycin G (2) 的全合成分别通过 25 和 23 步完成，从 5-benzyloxy-2,4-dimethoxy-3-methyl-benzyl 醇. 该合成具有底物可调的立体选择性分子内 Pictet-Spengler 型反应，用于构建两个目标的关键五环核心，在 C-3 处具有天然构型或差向异构构型。通过使用 C-3 表五环框架，还成功合成了 3-epi-jorumycin (32) 和 3-epi-renieramycin G (34)。此外，对 3-epi-jorumycin (32) 的初步生物学评估，以及相关的合成中间体，表明这些化合物具有显着的细胞毒性。所以，

DOI：

10.1021/ja0535918

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文献信息

[EN] METHODS FOR PREPARING BIS-TETRAHYDROISOQUINOLINE-CONTAINING COMPOUNDS<br/>[FR] PROCÉDÉS DE PRÉPARATION DE COMPOSÉS CONTENANT BIS-TÉTRAHYDROISOQUINOLINE

申请人：CALIFORNIA INST OF TECHN

公开号：WO2019018539A1

公开（公告）日：2019-01-24

(-)-Jorumycin, ecteinascidin 743, saframycin A and related compounds, methods of preparing the same, formulations comprising the compounds, and methods of treating proliferative diseases with the same are provided.

(-)-Jorumycin、Ecteinascidin 743、Saframycin A 及相关化合物，以及这些化合物的制备方法、包含这些化合物的制剂，以及使用这些化合物治疗增生性疾病的方法均被提供。
Total synthesis and cytotoxicity of (−)-jorumycin and its analogues

作者：Wei Liu、Xiangwei Liao、Wenfang Dong、Zheng Yan、Nan Wang、Zhanzhu Liu

DOI：10.1016/j.tet.2012.02.016

日期：2012.4

(-)-Jorumycin and its 15 C-22 analogues were prepared employing L-tyrosine as the chiral starting material via 21 steps. These analogues, along with (-)-jorumycin itself, were evaluated in vitro for cytotoxicity against HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-823, Hela, HELF, and KB cells. The IC50 values of the cytotoxicity of most of these analogs were at the level of nM, which was similar to that of (-)-jorumycin. Among these analogs including (-)-jorumycin, hippuric acid ester derivative 23 exhibited the most potent and broad-spectrum cytotoxic activity against the ten cell lines with an average IC50 of 2.12 nM. (C) 2012 Elsevier Ltd. All rights reserved.

（-）-Jorumycin及其15C-22衍生物通过21步合成路线，利用L-酪氨酸作为手性起始材料制备而成。这些类似物，连同（-）-Jorumycin本身，在体外对HCT-8、BEL-7402、Ketr3、A2780、MCF-7、A549、BGC-823、Hela、HELF和KB细胞进行了细胞毒性评价。大部分类似物的细胞毒性IC50值均在nM水平，与（-）-Jorumycin相当。在这些类似物（包括（-）-Jorumycin）中，衍生物23对10种癌细胞显示出最显著和广谱的细胞毒性，平均IC50值为2.12nM。版权（C）2012 Elsevier Ltd. 所有权利保留。
Asymmetric Total Synthesis of (−)-Jorunnamycins A and C and (−)-Jorumycin from <scp>l</scp>-Tyrosine

作者：Ruijiao Chen、Hao Liu、Xiaochuan Chen

DOI：10.1021/np400538q

日期：2013.9.27

to these important antitumor alkaloids with high yields: (−)-jorunnamycin A, as a common precursor to other renieramycin-type alkaloids and their analogues, is obtained with 18.1% overall yield from l-tyrosine.

通过一种新的收敛方法合成了三种瑞尼霉素型抗肿瘤生物碱（-）-香run霉素A（1）和C（2）和（-）-jorumycin（3），该方法具有高度区域选择性和立体选择性Pictet- Spengler环化反应将异喹啉和三取代的苯丙氨醇伴侣偶联。这种合成策略使人们可以经济高效地获得这些重要的抗生物碱生物碱：（-）-柔润霉素A作为其他雷尼霉素类生物碱及其类似物的常见前体，可从1-酪氨酸中获得18.1％的总收率。
Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis

作者：Eric R. Welin、Aurapat Ngamnithiporn、Max Klatte、Guillaume Lapointe、Gerit M. Pototschnig、Martina S. J. McDermott、Dylan Conklin、Christopher D. Gilmore、Pamela M. Tadross、Christopher K. Haley、Kenji Negoro、Emil Glibstrup、Christian U. Grünanger、Kevin M. Allan、Scott C. Virgil、Dennis J. Slamon、Brian M. Stoltz

DOI：10.1126/science.aav3421

日期：2019.1.18

jorumycin and the closely related jorunnamycin A that deliberately diverges from the putative biosynthetic pathway underlying prior chemical syntheses. This route, which hinges on a carefully optimized asymmetric catalytic hydrogenation, can be easily modified to introduce unnatural structural diversity for functional optimization in further drug discovery research. Science, this issue p. 270 A route to two

Jorumycin 之旅 Jorumycin 是一种结构复杂的五环有机化合物，由海洋软体动物产生。类似化合物曲贝替定在治疗某些类型的癌症方面取得的成功使人们的注意力集中在探索乔鲁霉素的药物特性上。韦林等人。开发了一种简洁的途径来合成 jorumycin 和密切相关的 jorunnamycin A，该途径故意偏离先前化学合成的假定生物合成途径。该路线取决于精心优化的不对称催化氢化，可以轻松修改以引入非自然结构多样性，以在进一步的药物发现研究中进行功能优化。科学，这个问题 p。270 两种不同于生物合成的海洋天然产物的途径使药物发现的结构多样化成为可能。双四氢异喹啉 (bis-THIQ) 天然产物除了具有很强的革兰氏阳性和革兰氏阴性抗生素特性外，还因其异常有效的抗癌活性而得到深入研究。这些复杂多环化合物的合成策略在很大程度上依赖于亲电芳香化学，例如模仿其生物合成途径的 Pictet-Spengler
A Concise and Practical Semisynthesis of Ecteinascidin 743 and (-)-Jorumycin

作者：Shanghu Xu、Guan Wang、Jinjin Zhu、Chuang Shen、Zhezhou Yang、Jun Yu、Zhong Li、Tanghuan Lin、Xun Sun、Fuli Zhang

DOI：10.1002/ejoc.201601409

日期：2017.2.3

Ecteinascidin 743 (an anticancer drug) was synthesized from safracin B in 14 steps in 1.5 % overall yield. The strategy involves the direct conversion of an aliphatic amino group into an acetoxy group. This synthetic approach was also used to synthesize (–)‐jorumycin (a promising anticancer candidate). (–)‐Jorumycin was prepared in six steps from safracin B in 24.1 % overall yield.

Ecteinascidin 743（一种抗癌药）是由沙弗拉菌素B分14步合成的，总收率为1.5％。该策略涉及将脂族氨基直接转化为乙酰氧基。这种合成方法还用于合成（–）-霉素（一种有前途的抗癌候选药物）。（–）-柔红霉素是从沙弗拉菌素B分六步制备的，总收率为24.1％。