alpha,beta-去氢洛伐他汀 | 109273-98-5

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 中文名称: alpha,beta-去氢洛伐他汀
• 中文别名: 脱水洛伐他汀；洛伐他汀杂质C
• 英文名称: dehydromonacolin K
• 英文别名: α,β-dehydrolovastatin；Dehydro Lovastatin；[(1S,3R,7S,8S,8aR)-3,7-dimethyl-8-[2-[(2R)-6-oxo-2,3-dihydropyran-2-yl]ethyl]-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate
• CAS: 109273-98-5
• 化学式: C₂₄H₃₄O₄
• 分子量: 386.532
• InChiKey: SPIVMHAGTHFLMO-OCAGQIGWSA-N

物化性质

• 熔点：
  126-129°C
• 沸点：
  530.5±50.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、二氯甲烷（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• WGK Germany：
  1

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
  洛伐他汀	lovastatin	75330-75-5	C24H36O5	404.547

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	dehydromonacolin J	——	C19H26O3	302.414
  ——	[(1S,3R,7S,8S,8aR)-8-[2-[(4R,6R)-4-(2-methoxy-2-oxoethyl)-3-[[4-(methylcarbamoyl)phenyl]methyl]-2-oxo-1,3-oxazinan-6-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate	714975-83-4	C35H48N2O7	608.775
  ——	[(1S,3R,7S,8S,8aR)-8-[2-[(4R,6R)-3-[[4-(2-hydroxypropan-2-yl)phenyl]methyl]-4-(2-methoxy-2-oxoethyl)-2-oxo-1,3-oxazinan-6-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate	714975-80-1	C36H51NO7	609.803
  ——	(S)-2-Methyl-butyric acid (1S,3R,7S,8S,8aR)-8-(2-{(4R,6R)-3-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-4-methoxycarbonylmethyl-2-oxo-[1,3]oxazinan-6-yl}-ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester	714975-78-7	C35H49NO8	611.776
  ——	[(1S,3R,7S,8S,8aR)-8-[2-[(4R,6R)-4-(2-methoxy-2-oxoethyl)-3-[(3-methoxyphenyl)methyl]-2-oxo-1,3-oxazinan-6-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate	714975-76-5	C34H47NO7	581.75

反应信息

• 作为反应物：
  描述：

  alpha,beta-去氢洛伐他汀 以 甲醇 为溶剂， 生成 [(1S,3R,7S,8S,8aR)-3,7-dimethyl-8-[2-[(4R,6R)-4-[2-(methylamino)-2-oxoethyl]-3-[[4-(methylcarbamoyl)phenyl]methyl]-2-oxo-1,3-oxazinan-6-yl]ethyl]-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate
  参考文献：
  名称：

  Statin-derived 1,3-oxazinan-2-ones as submicromolar inhibitors of LFA-1/ICAM-1 interaction: stabilization of the metabolically labile vanillyl side chain

  摘要：

  Modification of the vanillyl substituent on a potent, semisynthetic lymphocyte function-associated antigen (LFA)1/intercellular adhesion molecule (ICAM)-1 binding inhibitor of the statin family resulted in metabolically more stable analogues that displayed submicromolar inhibitory activity in vitro and considerable anti-inflammatory activity in vivo. The benzodioxole derivative 2b emerged with the best overall profile. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.006
• 作为产物：
  描述：

  洛伐他汀 在 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以100%的产率得到alpha,beta-去氢洛伐他汀
  参考文献：
  名称：

  土曲霉突变体对环状九环的转化阻止了lovA和lovC基因的洛伐他汀生物合成。

  摘要：

  检查了具有lovC或lovA基因被破坏的两个曲霉曲霉突变体的能力，这些突变体可将九肽转化为洛伐他汀1（一种降胆固醇药物）。lovC破坏剂能够有效地将二氢莫纳可林L 5或莫纳可林J 9转化为1，还可以将去甲基莫纳可林J 15转化为紧致蛋白3。相反，lovA突变体具有意想不到的活性β-氧化系统，仅产生少量的1在加入直接前体9后，大部分添加的非核苷酸都降解为庚肽22。类似地，lovA突变体不会积聚聚酮化合物合酶产物5，并通过两个β-氧化和β-环化反应迅速降解了作为前体添加的任何5。在C-6处羟基化得到20。

  DOI：

  10.1039/b207721c

文献信息

• Cytotoxic Dehydromonacolins from Red Yeast Rice
  作者：Lin Zhu、Lee-Fong Yau、Jing-Guang Lu、Guo-Yuan Zhu、Jing-Rong Wang、Quan-Bin Han、Wen-Luan Hsiao、Zhi-Hong Jiang

  DOI：10.1021/jf203579f

  日期：2012.2.1

  Two new dehydromonacolins (1 and 3), together with nine known monacolins (4-12), were isolated from red yeast rice. Compounds 4-6 were isolated from a natural resource for the first time. Their structures were elucidated by means of NMR and mass spectroscopic analyses. The structure of dehydromonacolin N (1) was further confirmed by its semisynthesis from monacolin K (lovastatin) (11). Dehydromonacolin J (2), an intermediate in the semisynthesis of 1, was obtained as a new dehydromonacolin. The structure of dehydromonacolin L (3) was also confirmed by an elimination reaction of monacolin L (12). Compound 1, possessing a C2 side chain, is unprecedented in the natural monacolin family and exhibited moderate cytotoxic activity against Hep G2, Caco-2, and MCF-7 cancer cell lines. Dehydromonacolin K (8) demonstrated the most potent cytotoxicity to all three of these cell lines. The structure activity relationship of natural and synthesized monacolins was discussed. This is the first report on the cytotoxic effects of dehydromonacolins.
• Convenient two-step stereospecific hydroxy-substitution with retention in β-hydroxy-δ-lactones. 4 ()-heterosubstituted mevinolin and -analogs
  作者：W. Bartmann、G. Beck、E. Granzer、H. Jendralla、B.V. Kerekjarto、G. Wess

  DOI：10.1016/s0040-4039(00)85044-3

  日期：1986.1
• Statin-derived 1,3-oxazinan-2-ones as submicromolar inhibitors of LFA-1/ICAM-1 interaction: stabilization of the metabolically labile vanillyl side chain
  作者：Thomas Ullrich、Karl Baumann、Karl Welzenbach、Simone Schmutz、Gian Camenisch、Josef G. Meingassner、Gabriele Weitz-Schmidt

  DOI：10.1016/j.bmcl.2004.03.006

  日期：2004.5

  Modification of the vanillyl substituent on a potent, semisynthetic lymphocyte function-associated antigen (LFA)1/intercellular adhesion molecule (ICAM)-1 binding inhibitor of the statin family resulted in metabolically more stable analogues that displayed submicromolar inhibitory activity in vitro and considerable anti-inflammatory activity in vivo. The benzodioxole derivative 2b emerged with the best overall profile. (C) 2004 Elsevier Ltd. All rights reserved.
• Transformations of cyclic nonaketides by Aspergillus terreus mutants blocked for lovastatin biosynthesis at the lovA and lovC genes
  作者：John L. Sorensen、Karine Auclair、Jonathan Kennedy、C. Richard Hutchinson、John C. Vederas

  DOI：10.1039/b207721c

  日期：2003.12.19

  Two mutants of Aspergillus terreus with either the lovC or lovA genes disrupted were examined for their ability to transform nonaketides into lovastatin 1, a cholesterol-lowering drug. The lovC disruptant was able to efficiently convert dihydromonacolin L 5 or monacolin J 9 into 1, and could also transform desmethylmonacolin J 15 into compactin 3. In contrast, the lovA mutant has an unexpectedly active

  检查了具有lovC或lovA基因被破坏的两个曲霉曲霉突变体的能力，这些突变体可将九肽转化为洛伐他汀1（一种降胆固醇药物）。lovC破坏剂能够有效地将二氢莫纳可林L 5或莫纳可林J 9转化为1，还可以将去甲基莫纳可林J 15转化为紧致蛋白3。相反，lovA突变体具有意想不到的活性β-氧化系统，仅产生少量的1在加入直接前体9后，大部分添加的非核苷酸都降解为庚肽22。类似地，lovA突变体不会积聚聚酮化合物合酶产物5，并通过两个β-氧化和β-环化反应迅速降解了作为前体添加的任何5。在C-6处羟基化得到20。