(+)-(2R,3S)-3-hydroxy-2,4-dimethylpentanoic acid | 77341-63-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (+)-(2R,3S)-3-hydroxy-2,4-dimethylpentanoic acid
• 英文别名: [2R,3S]-(+)-3-hydroxy-2,4-dimethylpentanoic acid；(2R,3S)-2,4-dimethyl-3-hydroxypentanoic acid；(2R,3S)-3-hydroxy-2,4-dimethylpentanoic acid
• CAS: 77341-63-0
• 化学式: C₇H₁₄O₃
• 分子量: 146.186
• InChiKey: ICRIJRMABYUYBG-RITPCOANSA-N

物化性质

• 熔点：
  75-76 °C
• 沸点：
  257.3±23.0 °C(Predicted)
• 密度：
  1.064±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 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：

  甲醇 、 (+)-(2R,3S)-3-hydroxy-2,4-dimethylpentanoic acid 在 盐酸 作用下， 反应 4.0h， 以86%的产率得到[2R,3S]-(+)-methyl-3-hydroxy-2,4-dimethyl-pentanoate
  参考文献：
  名称：

  使用基于（S，S）-（+）-伪麻黄碱的酰胺的不对称羟醛反应：立体选择性合成α-甲基-β-羟基酸，酯，酮以及1,3-Syn和1,3-抗二醇

  摘要：

  报道了进行立体选择性醛醇缩合反应的非常有效的方法。（S，S）-（+）-伪麻黄碱衍生的丙酰胺烯醇化物与几种醛的反应仅以良好的收率仅产生了四种可能的非对映异构体之一，尽管先生成的烯醇酸锂与锆（​​II）盐进行了重金属化。为了获得高的顺式选择性，添加醛是必需的。如此形成的顺-α-甲基-β-羟基酰胺被转化为其他有价值的手性非外消旋合成子，例如α-甲基-β-羟基酸，酯和酮。最后，已经开发了一种立体控制的还原程序，该程序从如此获得的α-甲基-β-羟基酮开始，可以合成1,3-syn-或1,3-抗-α-甲基-1，

  DOI：

  10.1021/jo000035h
• 作为产物：
  描述：

  N-<(2R,3S)-3-hydroxy-2,4-dimethylpentanoyl>-(1S,5R,7R)-10,10-dimethyl-3-thioxo-2-aza-4-oxatricyclo<5.2.1.0^1,5>decane 在 4-二甲氨基吡啶 、 水 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到(+)-(2R,3S)-3-hydroxy-2,4-dimethylpentanoic acid
  参考文献：
  名称：

  A novel DMAP-promoted oxazolidinethione deacylation. Application for the direct conversion of the initial chiral thioimide aldols to various ester protecting groups

  摘要：

  DMAP (4-(dimethylamino)pyridine) promoted nucleophilic cleavage of the initial chiral thioimide aldols can be directed to form various ester protecting groups without causing racemization of the newly created stereocenters. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00710-8

文献信息

• [EN] SUBSTITUTED TETRAHYDROFURANS AS MODULATORS OF SODIUM CHANNELS<br/>[FR] TÉTRAHYDROFURANES SUBSTITUÉS EN TANT QUE MODULATEURS DE CANAUX SODIQUES
  申请人：VERTEX PHARMA

  公开号：WO2021113627A1

  公开（公告）日：2021-06-10

  Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.

  提供了作为钠通道抑制剂的化合物及其药用盐。还提供了包含这些化合物或药用盐的药物组合物，以及使用这些化合物、药用盐和药物组合物治疗各种疾病，包括疼痛的方法。
• Highly stereoselective titanium-mediated aldol reactions from chiral α-silyloxy ketones. A reliable tool for the synthesis of natural products
  作者：Judit Esteve、Carme Jiménez、Joaquim Nebot、Javier Velasco、Pedro Romea、Fèlix Urpí

  DOI：10.1016/j.tet.2011.06.019

  日期：2011.8

  Chiral α-silyloxy ketones participate in highly stereoselective TiCl4-mediated aldol reactions that afford diastereomerically pure syn–syn adducts in high yield irrespective of the R1 and R2 substituents flanking the carbonyl or the silicon protecting group. Further manipulation of the resulting aldol adducts provide in a straightforward manner highly functionalized fragments that facilitate the synthesis

  手性α-甲硅烷氧基酮参与高度立体选择性的TiCl 4介导的醛醇缩合反应，无论羰基或硅保护基旁的R 1和R 2取代基如何，都能以高收率获得非对映体纯的syn - syn加合物。所得醛醇加合物的进一步处理以直接的方式提供了高度官能化的片段，其促进了天然产物的合成。
• Oxazinanones as chiral auxiliaries: synthesis and evaluation in enolate alkylations and aldol reactions
  作者：Stephen G. Davies、A. Christopher Garner、Paul M. Roberts、Andrew D. Smith、Miles J. Sweet、James E. Thomson

  DOI：10.1039/b604073j

  日期：——

  Homochiral beta-amino esters (prepared on multigram scale by lithium amide conjugate addition) are readily transformed into oxazinanones. N-acyl derivatives of oxazinanones undergo stereoselective enolate alkylation reactions, with higher stereoselectivities observed for the enolate alkylation of (R)-N-propanoyl-4-iso-propyl-6,6-dimethyl-oxazinan-2-one than the corresponding Evans oxazolidin-2-one

  高手性β-氨基酯（通过酰胺锂共轭物的加成以克数制）很容易转化为恶二酮。恶唑烷酮的N-酰基衍生物经历立体选择性烯酸酯烷基化反应，与相应的Evans相比，（R）-N-丙酰基-4-异丙基-6,6-二甲基-恶嗪烷-2-酮的烯酸酯烷基化观察到更高的立体选择性。恶唑烷-2-酮。恶唑烷酮内的AC（4）-异丙基立体定向基团比类似的C（4）-苯基取代基具有更高的立体选择性。恶唑烷酮骨架内的C（6）处的宝石二甲基取代促进水解时的排他性外环裂解，从而以高收率提供α-取代的羧酸衍生物和母体恶嗪酮。一系列芳香族和脂肪族醛与（R）-N-丙酰基-4-异丙基-6,6-二甲基-恶二嗪-2-酮的氯钛烯酸酯的不对称醛醇缩合反应具有出色的非对映选择性。醛醇缩合产物的水解得到同手性的α-甲基-β-羟基-羧酸。
• Protocols for the preparation of each of the four possible stereoisomeric .alpha.-alkyl-.beta.-hydroxy carboxylic acids from a single chiral aldol reagent
  作者：Nanine A. Van Draanen、Simeon Arseniyadis、Michael T. Crimmins、Clayton H. Heathcock

  DOI：10.1021/jo00007a043

  日期：1991.3

  Protocols have been devised whereby all four possible stereoisomeric alpha-alkyl-beta-hydroxy carboxylic acids can be derived from a single aldol reagent, hydroxy ketone 3. Compound 3, obtained in enantiomerically homogeneous form in 50% overall yield from tert-butylglycine (1), is used for aldol reactions in the form of its trimethylsilyl and tert-butyldimethylsilyl derivatives, 4 and 5. The Z lithium and Z boron enolates of 4 react with various aldehydes to give aldols 8 and 9, respectively. Deprotonation of 4 by bromomagnesium 2,2,6,6-tetramethylpiperidide (MTMP) gives the E enolate, which may be trapped by trimethylsilyl chloride to obtain the E silyl enol ether 11. The E bromomagnesium enolate of 4 reacts with aldehydes to give aldols of structure 15. Transmetalation of the bromomagnesium enolate of keto ether 5 is accomplished by reaction with (triisopropoxy)titanium chloride. The resulting E (triisopropoxy)titanium enolate reacts with aldehydes to provide aldols of structure 17. The aldols resulting from the foregoing reactions are hydrolyzed to keto diols 19-22, which are oxidized to the stereoisomeric alpha-methyl-beta-hydroxy carboxylic acids 23-26.
• Synthesis of a new fluorinated oxazolidinone and its reactivity as a chiral auxiliary in Aldol reactions
  作者：Santos Fustero、Julio Piera、Juan F. Sanz-Cervera、Paula Bello、Natalia Mateu

  DOI：10.1016/j.jfluchem.2007.03.001

  日期：2007.6

  A new enantiomerically pure fluorinated oxazolidinone has been prepared from a fluorinated imidoyl chloride and an optically pure sulfoxide. The diastereoselective reduction of the beta-iminosulfoxide thus formed followed by elimination of the sulfoxide and cyclization of the created aminoalcohol furnishes the desired product. The fluorinated oxazolidinone was subsequently used as a chiral auxiliary in Aldol reactions. We also found that the selective formation of the syn-Evans and syn-non-Evans diastereoisomer can be controlled by adjusting the Lewis acid/base ratio. (c) 2007 Elsevier B.V. All rights reserved.