(+/-)-2-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid | 460352-32-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (+/-)-2-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid
• 英文别名: 2-hydroxy-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)acetic acid；2-Hydroxy-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)acetic acid
• CAS: 460352-32-3
• 化学式: C₁₆H₂₂O₃
• 分子量: 262.349
• InChiKey: RMZVGANQMYNRAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-2-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid 在 sodium hydroxide 作用下， 以 水 、 异丙醇 为溶剂， 生成 (R)-2-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid
  参考文献：
  名称：

  A Practical Synthesis of the RAR_γ Agonist, BMS-270394

  摘要：

  A novel synthesis of 1 (BMS-270394), a nuclear retinoic acid receptor (RARgamma) agonist, is reported. The synthesis includes an enantioselective reduction of alpha-ketoacid 4 to the corresponding chiral a.-hydroxy acid 7 using a NaBH4/L-tartaric acid mixture and a novel coupling between 7 and an electron-deficient aniline 11 which was activated via N-sulfinyl derivative 15 to form chiral alpha-hydroxy amide 16. The synthesis was completed by a racemization-free hydrolysis of 16 to the corresponding alpha-hydroxy amidoacid 1 using KOPSiMe3 in acetonitrile.

  DOI：

  10.1021/op0202134
• 作为产物：
  描述：

  ethyl 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetate 在 lithium hydroxide 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 3.0h， 生成 (+/-)-2-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid
  参考文献：
  名称：

  Enantioselective microbial reduction of 2-oxo-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′-naphthalenyl)acetic acid and its ethyl ester

  摘要：

  The chiral ester ethyl (2R)-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl) acetate 2 and the corresponding acid 4 were prepared as intermediates in the synthesis of the retinoic acid receptor gamma-specific agonist (R)-3-fluoro-4-[[hydroxy(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)acety]amino]benzoic acid 7. Enantioselective reduction of ethyl 2-oxo-2-(1',2',3',4'-tetrahydro-1'.1',4',4'-tetramethyl-6'-naphthalenyl)acetate 1 to alcohol 2 was carried out using Aureobasidium pullulans SC 13849 in 98% yield and with an enantiomeric excess (e.e.) of 96%. Among microorganisms screened for the reduction of 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid 3 to hydroxy acid 4. Candida maltosa SC 16112 and two strains of Candida utilis (SC 13983, SC 1394) gave reaction yields of >53% with e.e.s. of >96%. (C) 2002 Elsevier Science Ltd, All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00109-x

文献信息

• COMPOSES BI-AROMATIQUES ET LEUR UTILISATION EN MEDECINE HUMAINE ET VETERINAIRE ET EN COSMETIQUE
  申请人：CENTRE INTERNATIONAL DE RECHERCHES DERMATOLOGIQUES GALDERMA - CIRD GALDERMA

  公开号：EP0552282A1

  公开（公告）日：1993-07-28
• [EN] BI-AROMATIC COMPOUNDS AND THEIR USE IN HUMAN AND VETERINARY MEDECINE AND IN COSMETIC PREPARATIONS
  申请人：——

  公开号：WO1992006948A1

  公开（公告）日：1992-04-30

  [EN] Bi-aromatic compounds of formula (I) wherein: Ar is either: (II) n = 1 or 2 or: (III) X is a divalent radical, Z is O, S or a divalent radical, and R1, R2, R3, R4 and R5 are an hydrogen atom or different organic radicals and the salts of compounds of formula (I) when R1 is a carboxylic acid function. For use in human and veterinary medecine and in cosmetic preparations.
  [FR] Composés bi-aromatiques répondant à la formule (I) dans laquelle: Ar représente soit (II), n = 1 ou 2, soit (III), X représente un radical divalent, Z représente O, S ou un radical divalent, et R1, R2, R3, R4 et R5 représentent un atome d'hydrogène ou différents radicaux organiques et les sels des composés de formule (I) lorsque R1 est une fonction acide carboxylique. Utilisation en médecine humaine et vétérinaire et en cosmétique.
• Enantioselective microbial reduction of 2-oxo-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′-naphthalenyl)acetic acid and its ethyl ester
  作者：Ramesh N Patel、Linda Chu、Ramakrishna Chidambaram、Jason Zhu、Joydeep Kant

  DOI：10.1016/s0957-4166(02)00109-x

  日期：2002.3

  The chiral ester ethyl (2R)-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl) acetate 2 and the corresponding acid 4 were prepared as intermediates in the synthesis of the retinoic acid receptor gamma-specific agonist (R)-3-fluoro-4-[[hydroxy(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)acety]amino]benzoic acid 7. Enantioselective reduction of ethyl 2-oxo-2-(1',2',3',4'-tetrahydro-1'.1',4',4'-tetramethyl-6'-naphthalenyl)acetate 1 to alcohol 2 was carried out using Aureobasidium pullulans SC 13849 in 98% yield and with an enantiomeric excess (e.e.) of 96%. Among microorganisms screened for the reduction of 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid 3 to hydroxy acid 4. Candida maltosa SC 16112 and two strains of Candida utilis (SC 13983, SC 1394) gave reaction yields of >53% with e.e.s. of >96%. (C) 2002 Elsevier Science Ltd, All rights reserved.
• A Practical Synthesis of the RAR_γ Agonist, BMS-270394
  作者：Ramakrishnan Chidambaram、Joydeep Kant、Jason Zhu、Jean Lajeunesse、Pierre Sirard、Peter Ermann、Peter Schierling、Peter Lee、David Kronenthal

  DOI：10.1021/op0202134

  日期：2002.9.1

  A novel synthesis of 1 (BMS-270394), a nuclear retinoic acid receptor (RARgamma) agonist, is reported. The synthesis includes an enantioselective reduction of alpha-ketoacid 4 to the corresponding chiral a.-hydroxy acid 7 using a NaBH4/L-tartaric acid mixture and a novel coupling between 7 and an electron-deficient aniline 11 which was activated via N-sulfinyl derivative 15 to form chiral alpha-hydroxy amide 16. The synthesis was completed by a racemization-free hydrolysis of 16 to the corresponding alpha-hydroxy amidoacid 1 using KOPSiMe3 in acetonitrile.