9α-hydroxyl-2α,5α,10β,14β-tetra-acetoxy-4(20),11(12)-taxadiene | 358778-59-3

• 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: 9α-hydroxyl-2α,5α,10β,14β-tetra-acetoxy-4(20),11(12)-taxadiene
• 英文别名: 9α-hydroxy-2α,5α,10β,14β-tetraacetoxy-4(20),11-taxadiene；9α-hydroxy-2α,5α,10β,14β-tetraacetoxytaxa-4(20),11-diene；[(1S,2S,3R,5S,8R,9R,10R,14S)-2,10,14-triacetyloxy-9-hydroxy-8,12,15,15-tetramethyl-4-methylidene-5-tricyclo[9.3.1.03,8]pentadec-11-enyl] acetate
• CAS: 358778-59-3
• 化学式: C₂₈H₄₀O₉
• 分子量: 520.62
• InChiKey: XTVRAXMVYLRZMZ-JOAJAEHSSA-N

物化性质

• 沸点：
  563.2±50.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9α-hydroxyl-2α,5α,10β,14β-tetra-acetoxy-4(20),11(12)-taxadiene 在 吡啶 、 4-二甲氨基吡啶 、 Abisidia coerulea IFO 4011 、 PDA medium 作用下， 以 乙醇 为溶剂， 反应 175.0h， 生成 14β-hydroxy-2α,5α,9α,10β-tetraacetoxy-taxa-4(20),11-diene
  参考文献：
  名称：

  Combined biotransformations of 4(20),11-taxadienes

  摘要：

  Taxuyunnanine C (1) and its analogs (2 and 3), the C-14 oxygenated 4(20), 11-taxadienes from callus Cultures of Taxus sp., were regio- and stereo-selectively hydroxylated at the 7 beta position by a fungus, Abisidia coerulea IFO 4011, and it was interesting that the longer the alkyl chain of the acyloxyl group at C-14 became, the higher the yield of 7 beta-hydroxylated product was. Besides the three 7 beta-hydroxylated products (5, 9, 17). other nine new products (7, 11, 12, 14, 15, 16, 18, 20 and 21) and six known products (4, 6 8, 10, 13 and 19) were obtained. Subsequently. the acetylated derivatives (24 and 27) of 7 beta- and 9 alpha-hydroxylated products of I were regio- and stereo-specifically hydroxylated at the 9 alpha position by Ginkgo cells and 7 position by A. coerulea, respectively. Thus, the two specific oxidations have been combined. These bioconversions would provide not only valuable intermediates for the semi-synthesis of paclitaxel or other bioactive taxoids front 1 and its analogs. but also some useful hints for the biosynthetic pathway of taxoid in the natural Taxus plant. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.03.136
• 作为产物：
  描述：

  taxuyunnanin C 在 Absidia coerulea IFO 4011 作用下， 反应 168000.0h， 生成 9α-hydroxyl-2α,5α,10β,14β-tetra-acetoxy-4(20),11(12)-taxadiene
  参考文献：
  名称：

  紫杉云南C衍生物作为多药耐药性调节剂在MDR癌细胞中的合成与构效关系。

  摘要：

  通过对紫杉云南碱C进行化学修饰和生物转化，获得了一系列在不同位置（如C-2，C-5，C-7，C-9，C-10或C-14）带有较大基团的新一代紫杉类化合物（1 ）及其类似物4、5和10。化合物3、5、6、8和9a对MDR 2780AD细胞中的钙黄绿素蓄积具有显着的活性。实际上，最有效的化合物9a在C-14处具有肉桂酰氧基，在C-10处具有羟基，实际上对于MDR 2780AD细胞中抗癌剂长春新碱的细胞蓄积是有效的。6和9a对紫杉醇，阿霉素和长春新碱的增强作用与维拉帕米对MDR 2780AD细胞的增强作用相同。因此，化合物6和9a可以调节癌细胞的多药耐药性。检查了这些化合物对人正常细胞系的细胞毒性（IC（50）），WI-38和癌细胞模型VA-13和HepG2。由于化合物6和8没有细胞毒性，因此它们有望成为MDR癌症逆转剂的先导化合物。相反，化合物3、5和9a在MDR 2780AD中表现出对VA-

  DOI：

  10.1016/j.bmcl.2007.04.030

文献信息

• Synthesis and structure–activity relationships of taxuyunnanine C derivatives as multidrug resistance modulator in MDR cancer cells
  作者：Toshiaki Hasegawa、Jiao Bai、Jungui Dai、Liming Bai、Junichi Sakai、Shigenori Nishizawa、Yuhua Bai、Midori Kikuchi、Mariko Abe、Takao Yamori、Akihiro Tomida、Takashi Tsuruo、Katsutoshi Hirose、Masayoshi Ando

  DOI：10.1016/j.bmcl.2007.04.030

  日期：2007.7

  the multidrug resistance of cancer cells. The cytotoxicity (IC(50)) of the compounds was examined against human normal cell line, WI-38, and cancer model cell lines, VA-13 and HepG2. Since compounds 6 and 8 had no cytotoxicity, they were expected to be lead compounds of MDR cancer reversal agents. On the contrary, compounds 3, 5, and 9a showed cell growth inhibitory activity toward VA-13 and/or HepG2

  通过对紫杉云南碱C进行化学修饰和生物转化，获得了一系列在不同位置（如C-2，C-5，C-7，C-9，C-10或C-14）带有较大基团的新一代紫杉类化合物（1 ）及其类似物4、5和10。化合物3、5、6、8和9a对MDR 2780AD细胞中的钙黄绿素蓄积具有显着的活性。实际上，最有效的化合物9a在C-14处具有肉桂酰氧基，在C-10处具有羟基，实际上对于MDR 2780AD细胞中抗癌剂长春新碱的细胞蓄积是有效的。6和9a对紫杉醇，阿霉素和长春新碱的增强作用与维拉帕米对MDR 2780AD细胞的增强作用相同。因此，化合物6和9a可以调节癌细胞的多药耐药性。检查了这些化合物对人正常细胞系的细胞毒性（IC（50）），WI-38和癌细胞模型VA-13和HepG2。由于化合物6和8没有细胞毒性，因此它们有望成为MDR癌症逆转剂的先导化合物。相反，化合物3、5和9a在MDR 2780AD中表现出对VA-
• Biotransformation of 2α,5α,10β,14β-tetra-acetoxy-4(20), 11-taxadiene by Ginkgo cell suspension cultures
  作者：Jungui Dai、Hongzhu Guo、Dandan Lu、Weihua Zhu、Dayong Zhang、Junhua Zheng、Dean Guo

  DOI：10.1016/s0040-4039(01)00836-x

  日期：2001.7

  subsequently used as a substrate for the bioconversion by Ginkgo cell cultures, and the product obtained was confirmed to be the same as 2, which suggested that 2 is biosynthesized from 1. Investigation on properties of the related enzymes responsible for the biotransformation reaction through the experimental techniques of cell-free culture and substrate/product concentration analysis revealed that the

  银杏细胞悬浮培养物用于生物转化2α，5α，10β，14β-四乙酰氧基-4（20），11-紫杉二烯。获得了两种新型化合物，其结构分别为9α-羟基-2α，5α，10β，14β-四乙酰氧基-4（20），11-紫杉二烯1和9α，10β-二羟基-2α，5α，14β-tri -乙酰氧基-4（20），11-紫杉二烯2，分别基于其物理和化学数据。随后将化合物1用作通过银杏细胞培养进行生物转化的底物，并确认获得的产物与2相同，这表明2是从1生物合成的。。通过无细胞培养的实验技术和底物/产物浓度分析研究负责生物转化反应的相关酶的性质，发现这些酶是细胞外的和组成性的。
• Substrate specificity for the hydroxylation of polyoxygenated 4(20),11-taxadienes by Ginkgo cell suspension cultures
  作者：Jungui Dai、Min Ye、Hongzhu Guo、Weihua Zhu、Dayong Zhang、Qiu Hu、Junhua Zheng、Dean Guo

  DOI：10.1016/s0045-2068(03)00063-4

  日期：2003.8

  Three C-14 oxygenated taxanes isolated from callus cultures of Taxus spp., 2alpha,5alpha,10beta,14beta-tetra-acetoxy-4(20), 11-taxadiene 3, 2alpha,5alpha,10beta-triacetoxy-14beta-propionyloxy-4(20),11-taxadiene 4, 2alpha,5alpha,10beta-triacetoxy-14beta-(2-methylbutyryl)-oxy-4(20),I I-taxadiene 5, and three deacetylated derivatives of 3, 10beta-hydroxy-2alpha,5alpha,14beta-triacetoxy-4(20),11-taxadiene 6, 14beta-hydroxy-2alpha,5alpha, 10beta-triacetoxy-4(20),11-taxadiene 7, 10beta,14beta-dihydroxy-2alpha,5alpha-diacetoxy-4(20),11-taxadiene 8, could all be regio- and stereo-selectively hydroxylated at the 9alpha-position by Ginkgo cell suspension cultures to yield a series of new 9alpha,14beta-dihydroxylated taxoids. The effects of functional groups, especially at C-14 of the substrates, on the biotransformation were also investigated. The results revealed that substrates with an acetoxyl group at C-14 could be more efficiently 9alpha-hydroxylated than those with a longer ester chain or a hydroxyl group at C-14. An acetoxyl or hydroxyl group at C-10 had no effect on the conversion rates of the substrates, but substrates with the hydroxyl group (compared with the acetoxyl analogues) could be converted into 9alpha-hydroxylated products more easily. (C) 2003 Elsevier Science (USA). All rights reserved.
• Regio- and stereo-selective biotransformation of 2α,5α,10β,14β-tetra-acetoxy-4(20), 11-taxadiene by Ginkgo cell suspension cultures
  作者：Jungui Dai、Min Ye、Hongzhu Guo、Weihua Zhu、Dayong Zhang、Qiu Hu、Junhua Zheng、Dean Guo

  DOI：10.1016/s0040-4020(02)00529-x

  日期：2002.7

  Ginkgo biloba cell suspension cultures were used to bioconvert sinenxan A, 2alpha,5alpha, 10beta, 14beta-tetra-acetoxy-4(20), 11-taxadiene, a taxoid isolated from callus tissue cultures of Taxus spp. Besides two major products, 9alpha-hydroxy-2alpha,5alpha,10beta,14beta-tetra-acetoxy-4(20), 11-taxadiene 1 and 9alpha,10beta-dihydroxy-2alpha,5alpha,14beta-triacetoxy-4(20), 11-taxadiene 2, additional six minor products were obtained and five of them identified as new compounds. On the basis of chemical and spectral data, their structures were identified as 9alpha,14beta-dihydroxy-2alpha,5alpha,10beta-triacetoxy-4(20), 11-taxadiene 3, 6alpha,10beta-dihydroxy-2alpha,5alpha,14beta-triacetoxy-4(20), 11-taxadiene 4, 6alpha,9alpha,10beta-trihydroxy-2alpha,5alpha,14beta-triacetoxy-4(20), 11-taxadiene 5, 9alpha,10beta-O-(propane-2,2-diyl)-2alpha,5alpha,14beta-triacetoxy-4(20), 11-taxadiene 6, 9alpha-hydroxy-2alpha,5alpha,10beta,14beta-tetra-acetoxy-4(20), 11-taxadiene formate 7, 10beta-hydroxy-2alpha,5alpha,9alpha,14beta-tetra-acetoxy-4(20), 11-taxadiene formate 8, respectively. Investigation of the properties of the enzymes responsible for the biocatalysis process of sinenxan A to I and 2 revealed that the enzymes were extracellular and constitutive. Using sinenxan A and the two major products (1 and 2) as indicators, the stage and concentration of sinenxan A added and the kinetics of the biotransformation reaction were investigated. The results showed that: (1) the optimal stage for sinenxan A addition was the logarithmic phase of the cell growth period, in which sinenxan A was almost completely bioconverted, and the biotransformation rates were up to 60 and 20% for 1 and 2, respectively; (2) the optimal concentration of sinenxan A added was 60 mg/L; (3) the substrate was mainly converted into 1 and 2 in the first 48 h after addition and then into the minor products. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Structural diversification of taxanes by whole-cell biotransformation
  作者：Jungui Dai、Runjiang Qu、Jian-hua Zou、Xiaoguang Chen

  DOI：10.1016/j.tet.2008.06.062

  日期：2008.8

  The structural diversification of four 4(20),11(12)-taxadienes (sinenxan A and its two derivatives, and yunanxane) by microbial/plant whole-cell enzymatic transformation has been achieved; 53 derivatives have been obtained, and 41 of them are new compounds. The occurred reactions exhibited diversity, including hydroxylation, epoxidation, oxidation, hydrolysis, acylation, O-alkylation, O-glycosylation, rearrangement, etc. In addition, one chemical derivative, 9 alpha-cinnamoyl sinenxan A from one enzymatic product 9 alpha-hydroxyl sinenxan A, displayed significant reversal activity toward three MDR tumor cell lines (A549/taxol, KB/VCR, and HCT-8). (C) 2008 Elsevier Ltd. All rights reserved.