10β-hydroxy-2α,5α14β-triacetoxytaxa-4(20),11(12)-diene | 157056-97-8

• 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: 10β-hydroxy-2α,5α14β-triacetoxytaxa-4(20),11(12)-diene
• 英文别名: 10β-hydroxy-2α,5α,14β-triacetoxy-4(20),11-taxadiene；10β-hydroxy-2α,5α,14β-triacetoxytaxa-4(20),11-diene；10-desacetyl taxuyunnanine C；10-deacetyltaxuyunnanine C；10-deacetyltaxuyunnanin C；10-deacetyl sinenxan A；10-desacetyltaxuyunnanin C；[(1S,2S,3S,5S,8S,10S,14S)-2,14-diacetyloxy-10-hydroxy-8,12,15,15-tetramethyl-4-methylidene-5-tricyclo[9.3.1.03,8]pentadec-11-enyl] acetate
• CAS: 157056-97-8
• 化学式: C₂₆H₃₈O₇
• 分子量: 462.584
• InChiKey: RAKDXBHPGCOTQG-SFPMZPPXSA-N

物化性质

• 沸点：
  528.3±50.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  99.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  10β-hydroxy-2α,5α14β-triacetoxytaxa-4(20),11(12)-diene 在 N-甲基吗啉氧化物 、 四丙基高钌酸铵 作用下， 以 二氯甲烷 为溶剂， 反应 10.17h， 以89.3%的产率得到10-oxo-2α,5α,14β-triacetoxytaxa-4(20),11(12)-diene
  参考文献：
  名称：

  紫杉二烯的微生物转化和代谢物的多药耐药肿瘤逆转活性

  摘要：

  2个taxadienes（微生物转化1，2）中的溶液单独地具有两个丝状真菌研究，小克银汉霉刺孢小克CGMCC 3.3400和黑曲霉CGMCC 3.1858，以及两个放线菌的污渍，灰色链霉菌CACC 200300和诺卡氏菌菊CGMCC 4.1182。总共获得21种产品，其中13种是新化合物。发生的反应表现出多样性，包括选择性羟基化，环氧化，氧化，脱甲基，乙酰化，脱乙酰基和O-烷基化，我们提出了可行的生物转化途径。药理评估的结果表明，化合物15与10μM紫杉醇共同给药时，对多药耐药性（MDR）肿瘤细胞系A549 /紫杉醇具有明显的逆转活性。这项研究提供了一种有用的方法来制备新的活性紫杉烷衍生物，这些衍生物很难通过化学手段获得。

  DOI：

  10.1016/j.tet.2012.09.091
• 作为产物：
  描述：

  taxuyunnanin C 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以36.3%的产率得到10β-hydroxy-2α,5α14β-triacetoxytaxa-4(20),11(12)-diene
  参考文献：
  名称：

  A Furantaxane with an Unusual 6/8/6/5 Ring System and Potent Tumor MDR Reversal Activity Obtained via Microbial Transformation

  摘要：

  A furantaxane (4) with an unusual 6/8/6/5 ring system and two hydroxylated products (2, 3) were isolated following the biotransformation of a taxane (1) by Streptomyces griseus. The structures of the isolates were elucidated by spectroscopic analysis. The absolute configuration of 4, which exhibited potent reversal activity in the A549/taxol MDR tumor cell line, was unambiguously deduced by single-crystal X-ray diffraction.

  DOI：

  10.1021/ol301755n

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-
• Microbial transformation of taxoids: Selective deacetylation and hydroxylation of 2α,5α,10β,14β-tetra-acetoxy-4(20), 11-taxadiene by the fungus Cunninghamella echinulata
  作者：Shanghui Hu、Xufang Tian、Weihua Zhu、Qicheng Fang

  DOI：10.1016/0040-4020(96)00426-7

  日期：1996.6

  The fungal genus Cunninghamella, in particular, Cunninghamella echinulata AS 3·1990 selectively transformed 2α,5α,10β,14β-tetra-acetoxy-4(20),11-taxadiene (1) to give 6α,10β-dihydroxy-2α,5α,14β-triacetoxy-4(20),11-taxadiene (2) in moderate yield (33%), along with 6β,10β-dihydroxy-2α,5α,14β-triacetoxy-4(20),11-taxadiene (3), 10β-hydroxy-2α,5α,14β-triacetoxy-taxadiene (4), hydroxy-4β,20-epoxy-2α,5α,

  真菌属Cunninghamella，尤其是Cunninghamella echinulata AS 3·1990选择性转化了2α，5α，10β，14β-四乙酰氧基-4（20），11-紫杉二烯（1）得到6α，10β-二羟基-2α，5α ，14β-三乙酰氧基-4（20），11-紫杉二烯（2）的收率中等（33％），以及6β，10β-dihydroxy-2α，5α，14β-triacetoxy-4（20），11-taxadiene（3），10β-羟基-2α，5α，14β-三乙酰氧基-紫杉二烯（4），羟基-4β，20-环氧-2α，5α，14β-三乙酰氧基-tax- 11-ene（5）。
• Synthesis and biological evaluation of taxinine analogues as orally active multidrug resistance reversal agents in cancer
  作者：Xin Zhao、Jun Gu、Dali Yin、Xiaoguang Chen

  DOI：10.1016/j.bmcl.2004.06.089

  日期：2004.9

  Three novel taxinine analogues were prepared and tested for their activity as multidrug resistance (MDR) reversal agents in comparison with verapamil. In vitro testing demonstrated that compounds 8-10 possess MDR-reversal activity in the KB/V cell line. Half-hour after treatment with 5, 10, and 20 mumol/L compound 9, the intracellular rhodamine 123 concentration increased 2.3, 2.9, and 3.2-fold, respectively, higher than 1.88-fold of 10 mumol/L verapamil in KB/V cell line. In vivo studies with VCR-resistant KB/V tumor xenografts showed that compound 9 in combination with VCR significantly inhibited tumor growth. Treatment with VCR or 9 alone did not result in growth inhibition. These results reveal that three taxinine analogues are good modifiers of MDR in tumor cells. (C) 2004 Elsevier Ltd. All rights reserved.
• 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.
• Special publicationfn1fn1Papers with this heading have received accelerated publication, due to their particular significance in the field of phytochemistry. Purification and characterization of acetyl coenzyme a: 10-hydroxytaxane O-acetyltransferase from cell suspension cultures of Taxus chinensis
  作者：Birgitta Menhard、Meinhart H Zenk

  DOI：10.1016/s0031-9422(98)00674-8

  日期：1999.3

  An O-acetyltransferase that catalyzes the regiospecific acetylation of a range of taxanes possessing an unsubstituted 10-hydroxyl group was detected and purified to apparent electrophoretic homogeneity from a cytosolic fraction of Taxus chinensis cell cultures. The purification involved negative calcium phosphate adsorption, sephadex desalting, DEAE, AcA44 chromatography, HighQ, CHT II, HiTrap Blue, Phenylsepharose and Mimetic Green purification steps. The purified acetyltransferase was found to be a monomeric protein of 71 +/- 1.5 kDa that is highly regio- and stereospecific towards the 10 beta-hydroxyl group of the taxane molecule and is also active towards 10-desacetylbaccatine III. The acetyltransferase reaction had a pH optimum of 9.0 with halfmaximal activities at pH 6.8 and 10.8, respectively. The temperature optimum was at 35 degrees C and the isoelectric point at 5.6. The apparent K-m values for 10-desacetyltaxuyunnanine C and acetyl CoA were 23 and 61 mu M, respectively. The turnover rate for the enzyme using both substrates was 0.2 mol mol(-1) of enzyme. The kinetic optimum was determined to be K-cat/K-m = 8.7 s(-1) L M-1. (C) 1999 Elsevier Science Ltd. All rights reserved.