(4R)-4,7,7-trimethyl-3-exo-(1-naphthyl)bicyclo<2.2.1>heptan-2-exo-yl (E)-7-phenyl-3,5-dioxo-6-heptenoate | 135942-64-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (4R)-4,7,7-trimethyl-3-exo-(1-naphthyl)bicyclo<2.2.1>heptan-2-exo-yl (E)-7-phenyl-3,5-dioxo-6-heptenoate
• 英文别名: [(1S,2R,3R,4S)-4,7,7-trimethyl-3-naphthalen-1-yl-2-bicyclo[2.2.1]heptanyl] (E)-3,5-dioxo-7-phenylhept-6-enoate
• CAS: 135942-64-2
• 化学式: C₃₃H₃₄O₄
• 分子量: 494.631
• InChiKey: IZSGWACZVOMIDB-UHJAPHFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R)-4,7,7-trimethyl-3-exo-(1-naphthyl)bicyclo<2.2.1>heptan-2-exo-yl (E)-7-phenyl-3,5-dioxo-6-heptenoate 在 sodium hydroxide 、 sodium tetrahydroborate 、 二乙基甲氧基硼烷 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 生成 4(S),6(S)-4-hydroxy-6-(2-phenylethyl)tetrahydropyran-2-one
  参考文献：
  名称：

  Enantioselective synthesis of .beta.-hydroxy .delta.-lactones: a new approach to the synthetic congeners of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors

  摘要：

  Chiral beta,delta-diketo esters derived from Taber's chiral alcohol or its enantiomer were reduced either in one step (Et2BOMe, NaBH4, THF-MeOH) or in two steps (2 equiv HAl(i-Bu)2, THF; Et2BOMe, NaBH4, THF-MeOH) to give syn-beta,delta-dihydroxy esters with high diastereoselectivity. Hydrolysis of the esters followed by lactonization afforded the title lactones of high optical purity ranging from 49 to > 97% ee.

  DOI：

  10.1021/jo00020a008
• 作为产物：
  描述：

  N-methoxy-N-methylcinnamamide 、 (ρ)-4,7,7-trimethyl-3-exo-(1-naphthyl)bicyclo<2.2.1>heptan-2-exo-yl acetoacetate 在 正丁基锂 、 sodium hydride 作用下， 生成 (4R)-4,7,7-trimethyl-3-exo-(1-naphthyl)bicyclo<2.2.1>heptan-2-exo-yl (E)-7-phenyl-3,5-dioxo-6-heptenoate
  参考文献：
  名称：

  Stereoselective Reduction ofβ,δ-Diketo Esters. A Novel Strategy for the Synthesis of Artificial HMG-CoA Reductase Inhibitors

  摘要：

  N-甲氧基-N-甲基酰胺与乙酰乙酸酯的二阴离子缩合，高产率地得到了β，δ-二酮酯，这些二酮酯在四氢呋喃-甲醇中与Et2BOMe-NaBH4还原，高度选择性地一步得到syn-β，δ-二羟基酯。类似地，Taber的手性醇或其对映体的β，δ-二酮酯分别还原得到中等对映体纯度的syn-β,δ-二羟基酯。通过先后使用二异丁基铝烷和Et2BOMe-NaBH4还原Taber的手性醇或其对映体的β,δ-二酮酯，获得了更高的非对映选择性和对映选择性。得到的syn-二醇酯经水解和内酯化得到多种常见于人工HMG-CoA还原酶抑制剂中的β-羟基-δ-内酯。

  DOI：

  10.1246/bcsj.68.350

文献信息

• Optically active esters of 7-substituted 3,5-difunctionalized 6-heptenoic acids
  申请人：SAGAMI CHEMICAL RESEARCH CENTER

  公开号：EP0475627A1

  公开（公告）日：1992-03-18

  An optically active ester of formula (I): wherein:    R is a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group or a substituted vinyl group;    Ar is a condensed aromatic group;    X¹ and Y¹ are not the same and each is a hydrogen atom or a hydroxyl group, or together represent an oxygen atom which forms a carbonyl group together with the carbon atom to which X¹ and Y¹ are attached; and    X² and Y² are not the same and each is a hydrogen atom or a hydroxyl group, or together represent an oxygen atom which forms a carbonyl group together with the carbon atom to which X² and Y² are attached, or an enantiomer thereof.

  化学式为（I）的光学活性酯，其中：R是取代或未取代的芳香基团，取代或未取代的杂环芳香基团或取代的乙烯基团；Ar是紧缩的芳香基团；X¹和Y¹不相同，每个都是氢原子或羟基，或者一起表示一个氧原子，该氧原子与X¹和Y¹连接的碳原子形成一个羰基基团；X²和Y²不相同，每个都是氢原子或羟基，或者一起表示一个氧原子，该氧原子与X²和Y²连接的碳原子形成一个羰基基团，或其对映异构体。
• A novel enantioselective synthesis of HMG Co-A reductase inhibitor NK-104 and a related compound
  作者：Tatsuya Minami、Tamejiro Hiyama

  DOI：10.1016/s0040-4039(00)60814-6

  日期：——

  Optically active methyl 6-oxo-3.5-syn-isopropylidenedioxyhexanoate (5) was prepared by enantioselective syn-reduction of beta,delta-diketo ester 2, followed by hydrolysis, protection of the diol moiety and ozonolysis, and was converted into a highly potent HMG Co-A reductase inhibitor NK-104 and an analogue.
• US5276154A
  申请人：——

  公开号：US5276154A

  公开（公告）日：1994-01-04
• Stereoselective Reduction of<i>β</i>,<i>δ</i>-Diketo Esters. A Novel Strategy for the Synthesis of Artificial HMG-CoA Reductase Inhibitors
  作者：Tamejiro Hiyama、Guntoori Bhaskar Reddy、Tatsuya Minami、Takeshi Hanamoto

  DOI：10.1246/bcsj.68.350

  日期：1995.1

  Condensation of N-methoxy-N-methyl amides with the dianions of acetoacetates gives in good yields β,δ-diketo esters, which are reduced with Et2BOMe–NaBH4 in tetrahydrofuran–methanol highly selectively to give syn-β,δ-dihydroxy esters in one step. Similarly, the β,δ-diketo esters of the Taber’s chiral alcohol or its enantiomer respectively are reduced to give syn-β,δ-dihydroxy esters of moderate enantiomeric excess. Higher diastereo- and enantioselectivity were achieved by reduction of the β,δ-diketo esters of the Taber’s chiral alcohol or its enantiomer successively with diisobutylalane and with Et2BOMe–NaBH4. The resulting syn-diol esters were hydrolyzed and lactonized to give various types of β-hydroxy-δ-lactones commonly found in artificial HMG-CoA reductase inhibitors.

  N-甲氧基-N-甲基酰胺与乙酰乙酸酯的二阴离子缩合，高产率地得到了β，δ-二酮酯，这些二酮酯在四氢呋喃-甲醇中与Et2BOMe-NaBH4还原，高度选择性地一步得到syn-β，δ-二羟基酯。类似地，Taber的手性醇或其对映体的β，δ-二酮酯分别还原得到中等对映体纯度的syn-β,δ-二羟基酯。通过先后使用二异丁基铝烷和Et2BOMe-NaBH4还原Taber的手性醇或其对映体的β,δ-二酮酯，获得了更高的非对映选择性和对映选择性。得到的syn-二醇酯经水解和内酯化得到多种常见于人工HMG-CoA还原酶抑制剂中的β-羟基-δ-内酯。
• Enantioselective synthesis of .beta.-hydroxy .delta.-lactones: a new approach to the synthetic congeners of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
  作者：G. Bhaskar Reddy、Tatsuya Minami、Takeshi Hanamoto、Tamejiro Hiyama

  DOI：10.1021/jo00020a008

  日期：1991.9

  Chiral beta,delta-diketo esters derived from Taber's chiral alcohol or its enantiomer were reduced either in one step (Et2BOMe, NaBH4, THF-MeOH) or in two steps (2 equiv HAl(i-Bu)2, THF; Et2BOMe, NaBH4, THF-MeOH) to give syn-beta,delta-dihydroxy esters with high diastereoselectivity. Hydrolysis of the esters followed by lactonization afforded the title lactones of high optical purity ranging from 49 to > 97% ee.