(4R,6R)-6-[2-[(1S,2S,8S,8aR)-1,2,6,7,8,8a-六氢-8-羟基-2-甲基-1-萘基]乙基]四氢-4-羟基-2H-吡喃-2-酮 | 58889-19-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 中文名称: (4R,6R)-6-[2-[(1S,2S,8S,8aR)-1,2,6,7,8,8a-六氢-8-羟基-2-甲基-1-萘基]乙基]四氢-4-羟基-2H-吡喃-2-酮
• 英文名称: 6-desmethylmonacolin J
• 英文别名: desmethylmonacolin J；ML-236A；ML-236-A；Compactin diol lactone；(4R,6R)-6-[2-[(1S,2S,8S,8aR)-8-hydroxy-2-methyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]ethyl]-4-hydroxyoxan-2-one
• CAS: 58889-19-3
• 化学式: C₁₈H₂₆O₄
• 分子量: 306.402
• InChiKey: WWSNTLOVYSRDEL-DZSDEGEFSA-N

物化性质

• 熔点：
  126-132 °C
• 沸点：
  535.2±50.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

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
  美伐他汀	mevastatin	73573-88-3	C23H34O5	390.52
  ——	(3R,5R)-7-[(1S,2S,8S,8aR)-8-hydroxy-2-methyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid	——	C18H28O5	324.417

反应信息

• 作为反应物：
  描述：

  (4R,6R)-6-[2-[(1S,2S,8S,8aR)-1,2,6,7,8,8a-六氢-8-羟基-2-甲基-1-萘基]乙基]四氢-4-羟基-2H-吡喃-2-酮 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 sodium;(3R,5R)-7-[(1S,2S,8S,8aR)-8-hydroxy-2-methyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate
  参考文献：
  名称：

  New Decalin Derivatives, Eujavanoic Acids A and B, from Eupenicillium javanicum

  摘要：

  Two new decalin derivatives, eujavanoic acids A (1) and B (2), were isolated from Eupenicillium javanicum, along with several compactin derivatives. The structures of 1 and 2 were determined by spectroscopic methods and modified Mosher's method. The side chain (2-methylbutanoyloxy) and acid functionalities of compactin derivatives were necessary to show the antifungal activity.

  DOI：

  10.1021/np040052s
• 作为产物：
  描述：

  美伐他汀 在 lithium hydroxide 作用下， 以 甲苯 为溶剂， 反应 25.0h， 生成 (4R,6R)-6-[2-[(1S,2S,8S,8aR)-1,2,6,7,8,8a-六氢-8-羟基-2-甲基-1-萘基]乙基]四氢-4-羟基-2H-吡喃-2-酮
  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

• Conversion of cyclic nonaketides to lovastatin and compactin by a lovc deficient mutant of Aspergillus terreus
  作者：Karine Auclair、Jonathan Kennedy、C.Richard Hutchinson、John C Vederas

  DOI：10.1016/s0960-894x(01)00290-6

  日期：2001.6

  Investigation of the post-PKS biosynthetic steps to the cholesterol-lowering agent lovastatin (1) using an Aspergillus terreus strain with a disrupted lovC gene, which is essential for formation of 4a,5-dihydromonacolin L (3), shows that 7 and 3 are precursors to 1, and demonstrates that lovastatin diketide synthase (lovF protein) does not require lovC. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus
  作者：Xuenian Huang、Yajing Liang、Yong Yang、Xuefeng Lu

  DOI：10.1016/j.ymben.2017.06.005

  日期：2017.7

  Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an industrial A. terreus strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete bioproduction of the cholesterol-lowering drug simvastatin feasible and promising.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• 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。
• New Decalin Derivatives, Eujavanoic Acids A and B, from <i>Eupenicillium </i><i>j</i><i>avanicum</i>
  作者：Shigeru Okamoto、Tomoo Hosoe、Takeshi Itabashi、Koohei Nozawa、Kaoru Okada、Galba Maria de Campos Takaki、Minoru Chikamori、Takashi Yaguchi、Kazutaka Fukushima、Makoto Miyaji、Ken-ichi Kawai

  DOI：10.1021/np040052s

  日期：2004.9.1

  Two new decalin derivatives, eujavanoic acids A (1) and B (2), were isolated from Eupenicillium javanicum, along with several compactin derivatives. The structures of 1 and 2 were determined by spectroscopic methods and modified Mosher's method. The side chain (2-methylbutanoyloxy) and acid functionalities of compactin derivatives were necessary to show the antifungal activity.