丁酸,2,2-二甲基-,(1S,3R,4R,4aR,7S,8S,8aR)-十氢-4-羟基-3,7-二甲基-8-[2-[(2R,4R)-四氢-4-羟基-6-羰基-2H-吡喃-2-基]乙基]-1-萘基酯 | 127343-06-0

• 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: 丁酸,2,2-二甲基-,(1S,3R,4R,4aR,7S,8S,8aR)-十氢-4-羟基-3,7-二甲基-8-[2-[(2R,4R)-四氢-4-羟基-6-羰基-2H-吡喃-2-基]乙基]-1-萘基酯
• 英文名称: 6(R)-<2-<8(S)-<(2,2-dimethylbutyryl)oxy>-2(S),6(R)-dimethyl-5(R)-hydroxy-1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphth-1(S)-yl>ethyl>-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one
• 英文别名: 6(R)-<2-<8(S)-<(2,2-dimethylbutyryl)oxy>-2(S),6(R)-dimethyl-5(R)-hydroxy-1,2,3,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)>ethyl>-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one；6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-5(R)-hydroxy-6(R)-methyl-1,2,3,4,4a(R),5, 6,7,8,8a(R)-decahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one；6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-5(R)-hydroxy-6(R)-methyl-1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one；6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S),6(R)-dimethyl-5(R)-hydroxy-,1,2,3,4,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6,-tetrahydro-2H-pyran-2-one；6(R)-(2-{8(S)-[(2,2-dimethylbutyryl)oxy]-2(S),6(R)-dimethyl-5(R)-hydroxy-1,2,3,4a(R),5,6,7,8,8a(R)-decahydronaphthyl-1(S)}ethyl)-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one；[(1S,3R,4R,4aR,7S,8S,8aR)-4-hydroxy-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-1-yl] 2,2-dimethylbutanoate
• CAS: 127343-06-0
• 化学式: C₂₅H₄₂O₆
• 分子量: 438.605
• InChiKey: SOAAQDRMUAREJG-QUZHLCRUSA-N

物化性质

• 熔点：
  142-143 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  575.9±50.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  辛伐他汀 在 Wilkinson's catalyst 咪唑 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 4 A molecular sieve 、 四丁基氟化铵 、 水 、 氢气 、 溶剂黄146 、 硫脲 、 pyridinium chlorochromate 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 67.58h， 生成 丁酸,2,2-二甲基-,(1S,3R,4R,4aR,7S,8S,8aR)-十氢-4-羟基-3,7-二甲基-8-[2-[(2R,4R)-四氢-4-羟基-6-羰基-2H-吡喃-2-基]乙基]-1-萘基酯
  参考文献：
  名称：

  3-羟基-3-甲基戊二酰辅酶a还原酶抑制剂。7.辛伐他汀的六氢萘部分的修饰：5-氧化的和5-氧杂的衍生物。

  摘要：

  通过氧合和氧杂取代对辛伐他汀2a中的六氢萘环5位进行修饰，得到了两个衍生物系列，分别在体外评估了对3-羟基-3-甲基戊二酰辅酶A还原酶的抑制作用，并在体内急性评估了其作为α-羟色胺抑制剂的口服效果大鼠的胆固醇生成。在选择用于进一步生物学评估的化合物中，3,4,4a，5-四氢2a的6个β-甲基-5-氧杂10和5个α-羟基16衍生物，以及16个的6个β-表观异构体14证明在胆甾醇胺引发的狗中作为降胆固醇药具有口服活性。随后在狗中进行的急性口腔新陈代谢研究表明，化合物14和16的峰值血浆药物活性和曲线下面积值比化合物10低，并导致选择14和16进行毒理学评估。

  DOI：

  10.1021/jm00112a027

文献信息

• Intermediates and processes in the preparation of 5-oxygenated HMG-COA
  申请人：Merck & Co., Inc.

  公开号：US04921974A1

  公开（公告）日：1990-05-01

  This invention relates to novel intermediates and novel processes for their preparation where said intermediates are useful in the preparation of 5'-oxygenated derivatives (I) of lovastation and analogs thereof at the 8'-acyl side chain and 6'-position of the polyhydronaphthyl ring. Derivatives (I) and analogs thereof are useful in treating hypercholesterolemia. ##STR1##

  这项发明涉及新型中间体及其制备的新型过程，其中所述中间体在制备洛伐他汀（lovastation）及其类似物的5'-氧化衍生物（I）时是有用的，在聚氢萘环的8'-酰基侧链和6'-位置。衍生物（I）及其类似物在治疗高胆固醇血症方面是有用的。
• Process for the desilylation of a 4-silyloxy-tetrahydro-pyran-2-one
  申请人：Merck & Co., Inc.

  公开号：US05650523A1

  公开（公告）日：1997-07-22

  A process is described for the removal of a silyl protecting group from the 4-hydroxy group of a tetrahydro-pyran-2-one moiety.

  描述了一种从四氢吡喃-2-酮基团的4-羟基中去除硅保护基的过程。
• Processes and intermediates for the preparation of 5-oxygenated HMG-COA reductase inhibitors
  申请人：MERCK & CO. INC.

  公开号：EP0451965A1

  公开（公告）日：1991-10-16

  This invention relates to novel intermediates and novel processes for their preparation where said intermediates are useful for the preparation of 5-oxygenated derivatives (I) of lovastatin and analogs thereof at the 8-acyl side chain and 6-position of the polyhydronaphthyl ring.

  本发明涉及新型中间体及其新型制备工艺，其中所述中间体可用于制备洛伐他汀的 5-氧代衍生物 (I) 及其在多氢萘环的 8-酰基侧链和 6-位上的类似物。
• Novel synthesis of mevinolin-related compounds. Large-scale preparation of HMG-CoA reductase inhibitor L-679,336
  作者：Ann E. DeCamp、Sander G. Mills、Alan T. Kawaguchi、Richard Desmond、Robert A. Reamer、Lisa DiMichele、R. P. Volante

  DOI：10.1021/jo00011a022

  日期：1991.5

  A novel synthetic route to a mevinolin-related HMG-CoA reductase inhibitor L-679,336 is described. The key features of the synthesis are a diastereoselective osmium tetraoxide catalyzed dihydroxylation reaction and a highly selective, phosphorus-mediated, pinacol-type rearrangement to give ketone 6. In situ multinuclear NMR experiments were used to gain a detailed understanding of the pinacol step. The above route was used for multikilogram preparation of the title compound. Also described are Lewis acid catalyzed rearrangement reactions of epoxide intermediates 4 and 5, as well as the intramolecular hydrosilylation reaction of deacylated olefinic substrates 17 and 18.
• CAMP, ANN E. DE;MILLS, SANDER G.;KAWAGUCHI, ALAN T.;DESMOND, RICHARD;REAM+, J. ORG. CHEM., 56,(1991) N1, C. 3564-3571
  作者：CAMP, ANN E. DE、MILLS, SANDER G.、KAWAGUCHI, ALAN T.、DESMOND, RICHARD、REAM+

  DOI：——

  日期：——