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

• 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.
• Molecular cloning and characterization of a cytochrome P450 taxoid 9á-hydroxylase in Ginkgo biloba cells
  作者：Nan Zhang、Zhentai Han、Guiling Sun、Angela Hoffman、Iain W. Wilson、Yanfang Yang、Qian Gao、Jianqiang Wu、Dan Xie、Jungui Dai、Deyou Qiu

  DOI：10.1016/j.bbrc.2013.12.104

  日期：2014.1

  Taxol is a well-known effective anticancer compound. Due to the inability to synthesize sufficient quantities of taxol to satisfy commercial demand, a biotechnological approach for a large-scale cell or cell-free system for its production is highly desirable. Several important genes in taxol biosynthesis are currently still unknown and have been shown to be difficult to isolate directly from Taxus, including the gene encoding taxoid 9 alpha-hydroxylase. Ginkgo biloba suspension cells exhibit taxoid hydroxylation activity and provides an alternate means of identifying genes encoding enzymes with taxoid 9 alpha-hydroxylation activity. Through analysis of high throughput RNA sequencing data from G. biloba, we identified two candidate genes with high similarity to Taxus CYP450s. Using in vitro cell-free protein synthesis assays and LC-MS analysis, we show that one candidate that belongs to the CYP716B, a subfamily whose biochemical functions have not been previously studied, possessed 9 alpha-hydroxylation activity. This work will aid future identification of the taxoid 9 alpha-hydroxylase gene from Taxus sp. (C) 2013 Elsevier Inc. 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.