(-)-(2R)-2-acetyl-8-benzyloxy-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol | 81504-96-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (-)-(2R)-2-acetyl-8-benzyloxy-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol
• 英文别名: (R)-(-)-2-Acetyl-5-methoxy-8-(benzyloxy)-1,2,3,4-tetrahydronaphthalen-2-ol；(-)-(2R)-2-acetyl-8-benzyloxy-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-ol；1-[(2R)-2-hydroxy-5-methoxy-8-phenylmethoxy-3,4-dihydro-1H-naphthalen-2-yl]ethanone
• CAS: 81504-96-3
• 化学式: C₂₀H₂₂O₄
• 分子量: 326.392
• InChiKey: TVQFGBNPRMVIQN-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-(2R)-2-acetyl-8-benzyloxy-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 4.5h， 生成 (R)-(-)-2-Acetyl-8-hydroxy-5-methoxy-1,2,3,4-tetrahydro-2-naphthalenol
  参考文献：
  名称：

  Anthracyclines. X. The enantiospecific synthesis of ( - )-(7R)-7-Acetyl-7-hydroxy- 4,4-dimethoxy-5,6,7,8-tetrahydronaphthalen-1(4H)-one; a type I chiral dienone for the synthesis of 7-Deoxydaunomycinone

  摘要：

  8-苄氧基-5-甲氧基-3,4-二氢萘-2-羧酸 (8-Benzyloxy-5-methoxy-3,4-dhydronaphthalene-2-carboxylic) 8-Benzyloxy-5-methoxy-3,4-dihydronaphthalene-2-carboxylic acid (34)是通过以下四个步骤制备的 5-甲氧基-8-羟基-3,4-二氢萘-1(2H)-酮。不饱和酸 不饱和酸 (34) 与(S)-脯氨酸乙酯在二环己基碳二亚胺存在下缩合，得到酰胺 (35) 在二环己基碳二亚胺存在下，不饱和酸 (34) 与(S)-脯氨酸乙酯缩合，得到酰胺 (35)。 内酯 (37)。用氢化三丁基锡进行脱溴反应，然后将内酯与甲硫醇反应生成溴内酯（37）。 内酯与甲基锂反应，得到 (-)-(2R)-2-乙酰基-8-苄氧基-5-甲氧基-1,2,3,4-四氢萘-2-醇。通过催化去除 催化加氢去除苄基醚，并用硝酸铊（III）氧化生成的苯酚。 硝酸铊（III）氧化除去苄基醚，得到标题手性二烯酮。

  DOI：

  10.1071/ch9841709
• 作为产物：
  描述：

  Methyl 5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoate 在 三乙基硅烷 、 aluminum amalgam 、 (-)-(8,8-Dimethoxycamphoryl)sulfonyl>oxaziridine 、 水 、 三溴化硼 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 potassium carbonate 、 二甲基亚砜 作用下， 以 二氯甲烷 、 丙酮 、 三氟乙酸 为溶剂， 反应 57.5h， 生成 (-)-(2R)-2-acetyl-8-benzyloxy-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol
  参考文献：
  名称：

  Asymmetric Synthesis of the AB Ring Segments of Daunomycin and 4-Demethoxydaunomycin

  摘要：

  Asymmetric hydroxylation of the potassium enolate of beta-keto ester 14, with (camphorsulfonyl)-oxaziridine (-)-7c [tetrahydro-9,9-dimethyl-8,8-dimethorry-4H-4a,7-methanooxazirino[3,2-i][2,1]-benzisothiazole 3,3-dioxide] affords alpha-hydroxy beta-keto ester (R)-(+)-15 in >95% ee. The high ee's are attributed to the fact that this enolate probably exists in one geometric form as a consequence of intramolecular chelation. Reduction of the ketone in 15 with triethylsilane and conversion of the ester group into the methyl ketone results in a highly efficient synthesis of the AB ring building block (R)-(-)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-napthol (3b), a key intermediate in the asymmetric synthesis of the antitumor agent 4-demethoxydaunomycin (1c). Selective deprotection of the 8-methoxy group in 3b with BBr3 gives 3a, important in the enantioselective synthesis of the clinically useful antitumor agent adriamycin (1b). Attempts to prepare 3a and 3b more directly by asymmetric hydroxylation of the enolates of methyl 5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoate (9) or the 8-benzyloxy derivative of 16 resulted in low ee's, attributable to the formation of E/Z enolate mixtures and increased steric congestion in the transition state for hydroxylation.

  DOI：

  10.1021/jo00084a042

文献信息

• Preparation of (–)-(7R)-7-acetyl-7-hydroxy-4,4-dimethoxy-5,6,7,8-tetrahydro-naphthalen-1(4H)-one, a chiral<scp>AB</scp>-synthon for anthracycline synthesis
  作者：Ronald N. Warrener、Paul S. Gee、Richard A. Russell

  DOI：10.1039/c39810001100

  日期：——

  The (–)-(R)-dienone (13) was prepared in 10 steps from the known 8-hydroxy-5-methoxy-2, 3-dihydronaphthalen-1(4H)-one (2), and the chirality at C(7) in (13) corresponds to that found at C(9) in the naturally occurring anthracyclines related to daunomycin.

  （–）-（（R）-二烯酮（13）是由10个步骤从已知的8-羟基-5-甲氧基-2、3-二氢萘-1（4 H）-一（2）制备的，其手性为（13）中的C（7）对应于在与道诺霉素相关的天然蒽环类中的C（9）中发现的C（7）。
• A high-yielding enantiospecific synthesis of (−)-7-deoxydaunomycinone
  作者：Richard A. Russell、Adrian S. Krauss、Ronald N. Warrener、Robert W. Irvine

  DOI：10.1016/s0040-4039(01)80201-x

  日期：——

  base-catalysed condensation of 4 (or 7)-methoxy-3-phenylsulfonyl phthalides with chiral bicyclic quinone monoketals, one of which occurs in 95% yield and forms the basis of the first enantiospecific total synthesis of (−)-7-deoxydaunomycinone (3).

  比较了4（或7）-甲氧基-3-苯基磺酰基邻苯二甲酸酯与手性双环醌单缩酮的碱催化缩合的两种区域特异性模式，其中一种产率为95％，构成了第一个对映体总合成的基础（-）-7-脱氧金刚烷酮（3）的合成。
• Anthracyclines. XII. The preparation of (—)-(7R)-7-Acetyl-7-(t-butyldimethylsilyoxy-1(4H)-one and (+)-(6R)-6-Acetyl-6-(t-butyldimethylsilyloxy)- 4,4-dimethoxy-5,6,7,8-tetrahydronaphthalene-1(4H)-one: an Improved Route to Chiral AB Synthons for 7-Deoxydaunomycinone
  作者：RA Russell、AS Krauss、RW Irvine、RN Warrener

  DOI：10.1071/ch9850179

  日期：——

  The title dienones (2) and (5) were prepared from the chiral alcohols (7a) and (7b) respectively. These key starting materials were in turn available from the reduction of 3-acetyl-5-benzyloxy-8-methoxy-1,2- dihydronaphthalene (6a) and 3-acetyl-8-benzyloxy-5-methoxy-1,2- dihydronaphthalene (6b) with lithium aluminium hydride modified with (—)-N- methylephedrine and N- ethylaniline . Chiral phase high-pressure liquid chromatography was used to analyse the enantioselectivity of these reductions which were shown to yield variable results depending upon the origin of the reducing agent.

  标题二烯酮 (2) 和 (5) 分别由手性醇 (7a) 和 (7b) 制备而成。这些关键的起始原料又是由 3-乙酰基-5-苄氧基-8-甲氧基-1,2-二氢萘 (6a) 和 3-乙酰基-8-苄氧基-5-甲氧基-1,2-二氢萘 (6b) 与经 (-)-N- 甲基麻黄碱和 N- 乙基苯胺修饰的氢化铝锂进行还原得到的。 手性相高压液相色谱法用于分析这些还原反应的对映体选择性，结果表明，不同还原剂的来源会产生不同的结果。
• The total synthesis of optically pure (9R,13S)- and (9R,13R)-7-deoxy-13-dihydrodaunomycinone
  作者：Richard A. Russell、Robert W. Irvine、Ronald N. Warrener

  DOI：10.1021/jo00359a041

  日期：1986.5
• Asymmetric Synthesis of the AB Ring Segments of Daunomycin and 4-Demethoxydaunomycin
  作者：Franklin A. Davis、Charles Clark、Anil Kumar、Bang-Chi Chen

  DOI：10.1021/jo00084a042

  日期：1994.3

  Asymmetric hydroxylation of the potassium enolate of beta-keto ester 14, with (camphorsulfonyl)-oxaziridine (-)-7c [tetrahydro-9,9-dimethyl-8,8-dimethorry-4H-4a,7-methanooxazirino[3,2-i][2,1]-benzisothiazole 3,3-dioxide] affords alpha-hydroxy beta-keto ester (R)-(+)-15 in >95% ee. The high ee's are attributed to the fact that this enolate probably exists in one geometric form as a consequence of intramolecular chelation. Reduction of the ketone in 15 with triethylsilane and conversion of the ester group into the methyl ketone results in a highly efficient synthesis of the AB ring building block (R)-(-)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-napthol (3b), a key intermediate in the asymmetric synthesis of the antitumor agent 4-demethoxydaunomycin (1c). Selective deprotection of the 8-methoxy group in 3b with BBr3 gives 3a, important in the enantioselective synthesis of the clinically useful antitumor agent adriamycin (1b). Attempts to prepare 3a and 3b more directly by asymmetric hydroxylation of the enolates of methyl 5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoate (9) or the 8-benzyloxy derivative of 16 resulted in low ee's, attributable to the formation of E/Z enolate mixtures and increased steric congestion in the transition state for hydroxylation.