methyl 2-hydroxy-3-methyl-3-phenylbutyrate | 77586-78-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 2-hydroxy-3-methyl-3-phenylbutyrate
• 英文别名: methyl 2-hydroxy-3-methyl-3-phenylbutanoate
• CAS: 77586-78-8
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: LBYLKOFRBWIVPK-UHFFFAOYSA-N

物化性质

• 沸点：
  170-180 °C(Press: 15 Torr)
• 密度：
  1.093±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-hydroxy-3-methyl-3-phenylbutyrate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以100%的产率得到2-hydroxy-3-methyl-3-phenylbutanoic acid
  参考文献：
  名称：

  Synthesis and Biological Activity of Analogues of the Antimicrotubule Agent N,β,β-Trimethyl-l-phenylalanyl-N-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N¹,3-dimethyl-l-valinamide (HTI-286)

  摘要：

  Hemiasterlin (1), a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286 (2), an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent antitumor effects, 2 has the advantage of circumventing the P-glycoprotein-mediated resistance that hampers the efficacy of other antimicrotubule agents such as paclitaxel and vincristine in animal models. This paper describes an in-depth study of the structure-activity relationships of analogues of 2, their effects on microtubule polymerization, and their in vitro and in vivo anticancer activity. Regions of the molecule necessary for potent activity are identified. Groups tolerant of modification, leading to novel analogues, are reported. Potent analogues identified through in vivo studies in tumor xenograft models include one superior analogue, HTI-042 (48).

  DOI：

  10.1021/jm040056u
• 作为产物：
  描述：

  methyl 3-phenyl-3-methyl-2-oxobutanoate 在 sodium tetrahydroborate 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 0.67h， 以80%的产率得到methyl 2-hydroxy-3-methyl-3-phenylbutyrate
  参考文献：
  名称：

  Compounds for treating tumors

  摘要：

  该发明提供了以下式（I）的化合物： 其中E、A、B′、R6、R7、R8和R9在规范中定义，这些化合物表现出抗癌活性，并可用于治疗癌症。

  公开号：

  US20050037977A1

文献信息

• Unambiguous Proof for Alcoxycarbonyl-group Migration inWagner-Meerwein Rearrangements
  作者：Daniel Berner、Hans Dahn、Pierre Vogel

  DOI：10.1002/hlca.19800630849

  日期：1980.12.10

  HSO3F/SO2ClF the β-hydroxy esters Ph-CHOH-CMe2-COOR (1, RMe, Et) are doubly protonated, then transformed into the fluorosulfates 7 and (partly) into the fluorides 8. At −15°, both 7 and 8 undergo a rearrangement, forming derivatives of Me2CC(Ph)COOR (2). By labelling 1 with 13C, singly (13C(3)) and doubly (13C(1,3)), it could be shown that exclusively the ROOC groups undergo a 1,2-shift. Compound 2 is also

  在HSO 3 F / SO 2 ClF中，将β-羟基酯Ph-CHOH-CMe 2 -COOR（1，RMe，Et）进行双质子化，然后转化为氟代硫酸盐7和（部分）转化为氟化物8。在-15 °，7和8均发生重排，形成Me 2 CC（Ph）COOR（2）的导数。通过标记1与13 C，单独使用（13 C（3））和双（13 C（1,3）），则可以示出专门的ROOC基团经历1,2-移。化合物2也在HSO 3 F / SO中形成通过消除，从异构体Me 2 COH-CHPh-COOR（3）中除去2 ClF ，并且不容易通过苯基1,2-移位从α-羟基酯Ph-CMe 2 -CHOH-COOR （5）中除去2 ClF 。另一个异构体Ph-C（OH）Me-CHMe-COOR （4）得到的产品与2不同。
• Compounds for treating tumors
  申请人：Zask Arie

  公开号：US20050037977A1

  公开（公告）日：2005-02-17

  The invention provides compounds of formula (I): wherein E, A, B′, R 6 , R 7 , R 8 , and R 9 are defined in the specification which compounds exhibit anticancer activity and are useful for treating cancer.

  该发明提供了以下式（I）的化合物： 其中E、A、B′、R6、R7、R8和R9在规范中定义，这些化合物表现出抗癌活性，并可用于治疗癌症。
• COMPOUNDS FOR TREATING TUMORS
  申请人：Zask Arie

  公开号：US20080221181A1

  公开（公告）日：2008-09-11

  The invention provides compounds of formula (I): wherein E, A, B′, R 6 , R 7 , R 8 , and R 9 are defined in the specification which compounds exhibit anticancer activity and are useful for treating cancer.

  本发明提供公式（I）的化合物：其中E，A，B'，R6，R7，R8和R9在说明书中定义，这些化合物表现出抗癌活性并可用于治疗癌症。
• Alkanoic acid derivatives and herbicidal compositions
  申请人：KUMIAI CHEMICAL INDUSTRY CO., LTD.

  公开号：EP0347811A1

  公开（公告）日：1989-12-27

  An alkanoic acid derivative of the formula: wherein R3 is a hydrogen atom, a halogen atom, a halogen-substituted alkyl group, an alkyl group, a cycloalkyl group, an alkylthioalkyl group, a hydroxyalkyl group, a hydroxyl group, a cyano group, an acyloxyalkyl group, a thienyl group, a naphthyl group, a dihydronaphthyl group or wherein R8 is a hydrogen atom, a halogen atom, a nitro group, an alkyl group, an alkoxy group or -S(O)nR9 wherein R9 is an alkyl group, and n is an integer of from 0 to 2, m is an integer of from 0 to 2, each of R2 and R4 which may be the same or different is a hydrogen atom or an alkyl group, or R2 and R4 form together with the adjacent carbon atom a 3-, 4-, 5- or 6-membered ring which may contain an oxygen atom and may be substituted by one or two alkyl groups, each of R5 and R6 which may be the same or different is a hydrogen atom or an alkyl group, R7 is an alkyl group or a phenyl group, or R6 and R7 form -(CH2)1- wherein ℓ is an integer of 3 or 4 which may be substituted by one or two alkyl groups, or R is an alkenyl group, a dihydronaphthyl group, a tetrahydronaphthyl group, a 1-oxo-1,2,3,4-tetrahydronaphthyl group, a 1,2-epoxycycloalkyl group or an indanyl group which may be substituted by an alkyl or alkoxy group; R1 is a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a phenyl group, an alkylideneamino group, an alkoxyalkyl group, an alkoxycarbonylalkyl group, a halogen-substituted alkyl group, a cycloalkyl group, a nitro-substituted phenylthioalkyl group, a halogen atom or a benzyl group which may be substituted by an alkyl or alkoxy group; or R and R1 form a ring; A is an alkyl group, an alkoxy group, an alkylthio group, a halogen atom, a halogen-substituted alkoxy group, an amino group, an alkylamino group or a dialkylamino group; B is a hydrogen atom, an alkyl group, an alkoxy group or a halogen-substituted alkoxy group; X is an oxygen atom or a sulfur atom; and Z is a methine group or a nitrogen atom; and a salt thereof.

  式中的烷酸衍生物： 其中 R3 是氢原子、卤素原子、卤素取代的烷基、烷基、环烷基、烷硫基、羟烷基、羟基、氰基、酰氧基烷基、噻吩基、萘基、二氢萘基或 其中 R8 为氢原子、卤素原子、硝基、烷基、烷氧基或-S(O)nR9，其中 R9 为烷基，且 n 为 0 至 2 的整数，m 为 0 至 2 的整数，R2 和 R4 可相同或不同，其中每个 R2 和 R4 为氢原子或烷基，或 R2 和 R4 与相邻碳原子一起形成 3、4、5 或 6 元环，该环可包含一个氧原子，并可被一个或两个烷基取代、R5 和 R6 可相同或不同，各自为氢原子或烷基，R7 为烷基或苯基，或 R6 和 R7 形成-(CH2)1-，其中 ℓ 为 3 或 4 的整数，可被一个或两个烷基取代、或 R 为烯基、二氢萘基、四氢萘基、1-氧代-1,2,3,4-四氢萘基、1,2-环氧环烷基或可被烷基或烷氧基取代的茚基；R1 是氢原子、烷基、烯基、炔基、苯基、亚烷基氨基、烷氧基烷基、烷氧羰基烷基、卤素取代的烷基、环烷基、硝基取代的苯硫基烷基、卤素原子或可被烷基或烷氧基取代的苄基；或 R 和 R1 形成一个环；A 是烷基、烷氧基、烷硫基、卤素原子、卤素取代的烷氧基、氨基、烷基氨基或二烷基氨基；B 是氢原子、烷基、烷氧基或卤素取代的烷氧基；X 是氧原子或硫原子；Z 是甲硫基或氮原子；及其盐。
• Kinetic Resolution of Racemic α-tert-Alkyl-α-hydroxy Esters by Enantiomer-Selective Carbamoylation
  作者：Nobuhito Kurono、Kentaro Ohtsuga、Masanori Wakabayashi、Tadahiro Kondo、Hirohito Ooka、Takeshi Ohkuma

  DOI：10.1021/jo201940w

  日期：2011.12.16

  Kinetic resolution of sterically hindered racemic alpha-tert-alkyl-alpha-hydroxy esters is performed by enantiomer-selective carbamoylation with the t-Bu-Box-Cu(II) catalyst (Box = bis(oxazoline)). The reaction with 0.5 equiv of n-C3H7NCO is carried out with a substrate-to-catalyst molar ratio of 500-5000 at -20 to 25 degrees C. The high enantiomer-discrimination ability of the catalyst achieves an excellent stereoselectivity factor (s = k(fast)/k(slow)) of 261 in the best case. A catalytic cycle for this reaction is proposed.