1-hydroxy-2-(1-hydroxypropan-2-yl)-8,8-dimethyl-6,7-dihydro-5H-phenanthrene-3,4-dione | 109664-02-0

• 物质功能分类: 有机原料 - 酮类化合物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 1-hydroxy-2-(1-hydroxypropan-2-yl)-8,8-dimethyl-6,7-dihydro-5H-phenanthrene-3,4-dione
• 英文别名: 5,6,7,8-tetrahydro-3-hydroxy-2-[(1R)-2-hydroxy-1-methylethyl]-8,8-dimethyl-1,4-phenanthrenedione；(+)-neocryptotanshinone；neocryptotanshinone
• CAS: 109664-02-0
• 化学式: C₁₉H₂₂O₄
• 分子量: 314.381
• InChiKey: PKEGICXVZMKJPR-JTQLQIEISA-N

物化性质

• 沸点：
  517.1±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  3.12
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  74.6
• 氢给体数：
  2.0
• 氢受体数：
  4.0

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

制备方法与用途

生物活性方面，Neo-cryptotanshinone 可从丹参（Salvia miltiorrhiza）中分离得到。这种化合物能够通过抑制 NF-κB 和 iNOS 信号途径，从而减轻由 LPS 引发的炎症反应。

反应信息

• 作为反应物：
  描述：

  1-hydroxy-2-(1-hydroxypropan-2-yl)-8,8-dimethyl-6,7-dihydro-5H-phenanthrene-3,4-dione 在 硫酸 作用下， 以 乙醇 为溶剂， 反应 0.75h， 以100%的产率得到隐丹参酮
  参考文献：
  名称：

  Aromatic Annulation Strategy for the Synthesis of Angularly-Fused Diterpenoid Quinones. Total Synthesis of (+)-Neocryptotanshinone, (-)-Cryptotanshinone, Tanshinone IIA, and (.+-.)-Royleanone

  摘要：

  The application of a photochemical aromatic annulation strategy in highly efficient total syntheses of several diterpenoid quinones isolated from the traditional Chinese medicine Dan Shen is reported. The pivotal step in each synthesis involves the assembly of a key tricyclic intermediate via the application of a recently developed ''second-generation'' photochemical aromatic annulation method for the construction of highly substituted aromatic systems. In the total synthesis of neocrypto-tanshinone,;the synthesis of the requisite diazo ketone annulation substrate 7 was achieved using palladium-mediated coupling reactions and an intramolecular Friedel-Crafts cyclization to form key carbon-carbon bonds. The pivotal aromatic annulation reaction was then accomplished by irradiating a solution of the diazo ketone 7 and the readily available siloxyalkyne 6 in benzene at room temperature. The desired tricyclic phenol 16 was produced in 58-65% yield and was then converted to (+)-neocryptotanshinone (1) by treatment with tetra-n-butylammonium fluoride in the presence of oxygen. Cyclization to generate (-)-cryptotanshinone (2) was accomplished in high yield by brief exposure of 1 to an ethanolic solution of concentrated sulfuric acid, and dehydrogenation of 2 with DDQ furnished tanshinone IIA (3). As a further demonstration of the utility of the photochemical aromatic annulation strategy in the construction of angularly-fused diterpenes, the total synthesis of(+/-)-royleanone (4) was also investigated. Irradiation of a solution of the diazo ketone 18 and siloxyalkyne 25 produced the tricyclic intermediate 26, which was converted in two steps to royleanone by desilylation and oxidation.

  DOI：

  10.1021/jo00131a006
• 作为产物：
  描述：

  隐丹参酮 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 以95%的产率得到1-hydroxy-2-(1-hydroxypropan-2-yl)-8,8-dimethyl-6,7-dihydro-5H-phenanthrene-3,4-dione
  参考文献：
  名称：

  丹参酮衍生物作为吲哚胺 2, 3-双加氧酶 1 和色氨酸 2, 3-双加氧酶双重抑制剂的发现和生物学评价

  摘要：

  吲哚胺 2, 3-双加氧酶 1 (IDO1) 和色氨酸 2, 3-双加氧酶 (TDO) 催化色氨酸-犬尿氨酸 (Trp-Kyn) 代谢途径的第一步和限速步骤，是癌症免疫治疗的有吸引力的靶点。文献中报道了一些双重 IDO1/TDO 抑制剂。然而，小分子 IDO1 和 TDO 抑制剂尚不能用于临床。在这里，我们报告了天然存在的萜类化合物丹参酮 IIA 和隐丹参酮的合成类似物，以及它们的 IDO1/TDO 抑制活性，使用酶促和细胞测定。最有效的化合物30分别通过表面等离子共振 (SPR)、酶动力学和光谱分析方法进一步表征了针对 IDO1 和 TDO 的直接相互作用、抑制动力学和不同结合模式。初步机制研究表明，30通过潜在的线粒体介导的 Bcl-2/Bax 通路显着促进细胞凋亡。IDO1 过表达的 HeLa 细胞模仿癌细胞，对30种治疗敏感。这些结果为传统草药的主要成分丹参酮的新临床应用提供了进一步的见解。

  DOI：

  10.1016/j.ejmech.2022.114294

文献信息

• Quinone Derivatives by Chemical Transformations of 16-Hydroxycarnosol from Salvia Species
  作者：Joaquín González Marrero、Lucía San Andrés、Javier Gutiérrez Luis

  DOI：10.1248/cpb.53.1524

  日期：——

  spectroscopic data of these semisynthetic diterpenes were identical to those given for the natural ones in the literature. These abietane diterpenes have very interesting biological activities and the semisynthetic approach described here represents an alternative to obtain them from other major diterpenes isolated from Salvia species. Additionally, seven new semisynthetic diterpene analogues, 11,14-dioxo-12,16-epoxy-8

  已知的二萜12,16-环氧香茅酚（2），异丹参酮II（6）和（+）-新隐丹参酮（8）是通过16-羟基香茅酚（1）的部分合成而获得的，16-羟基香茅酚（1）是相对分离的C-16羟基化松香二萜丹参的地上部分丰富。这些半合成二萜的物理和光谱数据与文献中对天然二萜的数据相同。这些松果二萜具有非常有趣的生物学活性，此处描述的半合成方法代表了从丹参属植物中分离的其他主要二萜获得它们的一种选择。此外，七个新的半合成二萜类似物，11,14-dioxo-12,16-epoxy-8,12-abietadien-20,7beta-olide（3），11,14-dioxo-12,16-epoxy-8,12 ，15（16）-松香三烯-20,7β-内酰胺（4），15,16-didehydro-12，
• Synthesis and vasodilative activity of tanshinone IIA derivatives
  作者：Yue-Feng Bi、Hai-Wei Xu、Xiao-Qing Liu、Xiao-Juan Zhang、Zhen-Ji Wang、Hong-Min Liu

  DOI：10.1016/j.bmcl.2010.06.076

  日期：2010.8

  A series of 2,2′-(substituted methylene)bis-(1,6,6-trimethyl-6,7,8,9-tetrahydrophenanthro[1,2-b]furan-10,11-dione) derivatives were synthesized by the reaction of tanshinone IIA (D1) and aromatic aldehyde in the presence of p-TsOH. Bromination derivative of D1 and hydrolysis product of cryptotanshinone (D2) were also prepared in this work. Vasodilation activity in vitro of them was valuated on the

  合成了一系列的2,2'-（取代亚甲基）双-（1,6,6-三甲基-6,7,8,9-四氢菲并[1,2 - b ]呋喃-10,11-二酮）衍生物丹参酮IIA（D 1）与芳香醛在对-TsOH的存在下反应的产物。这项工作中还制备了D 1的溴化衍生物和隐丹参酮（D 2）的水解产物。首次评价了Wistar大鼠血管胸主动脉平滑肌的收缩反应，评价了它们的体外血管舒张活性。他们中的大多数对去甲肾上腺素的收缩反应表现出浓度依赖性的抑制作用。
• Neocryptotanshinone protects against myocardial ischemia-reperfusion injury by promoting autolysosome degradation of protein aggregates via the ERK1/2-Nrf2-LAMP2 pathway
  作者：Ye Yang、Mingyan Shao、Junkai Yao、Shuangjie Yang、Wenkun Cheng、Lin Ma、Weili Li、Jing Cao、Yawen Zhang、Yueyao Hu、Chun Li、Yong Wang、Wei Wang

  DOI：10.1016/j.phymed.2022.154625

  日期：2023.2

  Purpose The current study aimed to investigate the molecular mechanism of NCTS involved in the therapeutic effect on I/R, with a special emphasis on the up-regulation of the ERK1/2-Nrf2-LAMP2 pathway to increase autolysosomal degradation during aggrephagy. Methods A rat model of myocardial I/R injury was constructed by left anterior descending (LAD) ligation-reperfusion. To verify cardiac protection, autolysosome

  背景 Aggrephagy 是消除由压力引起的错误折叠蛋白质的关键补偿机制，并且取决于蛋白质聚集体的自溶酶体降解。然而，关于心肌缺血/再灌注（I/R）损伤中聚集自噬相关的机制研究却很少。Neocryptotanshinone (NCTS) 是一种从丹参中提取的脂溶性活性化合物，可能对 I/R 具有心脏保护作用。然而，NCTS对I/R的疗效和具体机制尚未研究。 目的 目前的研究旨在研究 NCTS 参与 I/R 治疗作用的分子机制，特别强调 ERK1/2-Nrf2-LAMP2 通路的上调以增加自噬过程中的自溶酶体降解。 方法 采用左前降支（LAD）结扎-再灌注法构建大鼠心肌I/R损伤模型。为了验证心脏保护、蛋白质聚集体的自溶酶体清除及其细胞内生物学机制，创建了氧-葡萄糖剥夺/恢复 (OGD/R) 诱导的 H9c2 心肌细胞模型。 结果 NCTS 被发现对 I/R 大鼠具有显着的心脏保护作用，这
• Aromatic Annulation Strategy for the Synthesis of Angularly-Fused Diterpenoid Quinones. Total Synthesis of (+)-Neocryptotanshinone, (-)-Cryptotanshinone, Tanshinone IIA, and (.+-.)-Royleanone
  作者：Rick L. Danheiser、David S. Casebier、Fariborz Firooznia

  DOI：10.1021/jo00131a006

  日期：1995.12

  The application of a photochemical aromatic annulation strategy in highly efficient total syntheses of several diterpenoid quinones isolated from the traditional Chinese medicine Dan Shen is reported. The pivotal step in each synthesis involves the assembly of a key tricyclic intermediate via the application of a recently developed ''second-generation'' photochemical aromatic annulation method for the construction of highly substituted aromatic systems. In the total synthesis of neocrypto-tanshinone,;the synthesis of the requisite diazo ketone annulation substrate 7 was achieved using palladium-mediated coupling reactions and an intramolecular Friedel-Crafts cyclization to form key carbon-carbon bonds. The pivotal aromatic annulation reaction was then accomplished by irradiating a solution of the diazo ketone 7 and the readily available siloxyalkyne 6 in benzene at room temperature. The desired tricyclic phenol 16 was produced in 58-65% yield and was then converted to (+)-neocryptotanshinone (1) by treatment with tetra-n-butylammonium fluoride in the presence of oxygen. Cyclization to generate (-)-cryptotanshinone (2) was accomplished in high yield by brief exposure of 1 to an ethanolic solution of concentrated sulfuric acid, and dehydrogenation of 2 with DDQ furnished tanshinone IIA (3). As a further demonstration of the utility of the photochemical aromatic annulation strategy in the construction of angularly-fused diterpenes, the total synthesis of(+/-)-royleanone (4) was also investigated. Irradiation of a solution of the diazo ketone 18 and siloxyalkyne 25 produced the tricyclic intermediate 26, which was converted in two steps to royleanone by desilylation and oxidation.
• Discovery and biological evaluation of tanshinone derivatives as potent dual inhibitors of indoleamine 2, 3-dioxygenase 1 and tryptophan 2, 3-dioxygenase
  作者：Jiangxin Liu、Jian Ren、Kun Yang、Shuang Chen、Xinni Yang、Qin-Shi Zhao

  DOI：10.1016/j.ejmech.2022.114294

  日期：2022.5

  Indoleamine 2, 3-dioxygenase 1 (IDO1) and tryptophan 2, 3-dioxygenase (TDO), catalyzing the first and rate-limiting step of tryptophan-kynurenine (Trp-Kyn) metabolism pathway, are the appealing targets for cancer immunotherapy. A few dual IDO1/TDO inhibitors are reported in literature. However, small-molecule IDO1 and TDO inhibitors are not yet available for clinical use. Here, we report synthetic

  吲哚胺 2, 3-双加氧酶 1 (IDO1) 和色氨酸 2, 3-双加氧酶 (TDO) 催化色氨酸-犬尿氨酸 (Trp-Kyn) 代谢途径的第一步和限速步骤，是癌症免疫治疗的有吸引力的靶点。文献中报道了一些双重 IDO1/TDO 抑制剂。然而，小分子 IDO1 和 TDO 抑制剂尚不能用于临床。在这里，我们报告了天然存在的萜类化合物丹参酮 IIA 和隐丹参酮的合成类似物，以及它们的 IDO1/TDO 抑制活性，使用酶促和细胞测定。最有效的化合物30分别通过表面等离子共振 (SPR)、酶动力学和光谱分析方法进一步表征了针对 IDO1 和 TDO 的直接相互作用、抑制动力学和不同结合模式。初步机制研究表明，30通过潜在的线粒体介导的 Bcl-2/Bax 通路显着促进细胞凋亡。IDO1 过表达的 HeLa 细胞模仿癌细胞，对30种治疗敏感。这些结果为传统草药的主要成分丹参酮的新临床应用提供了进一步的见解。