tert-butyl (4R)-4-(hydroxymethyl)-2,2,4-trimethyl-1,3-oxazolidine-3-carboxylate | 219567-09-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: tert-butyl (4R)-4-(hydroxymethyl)-2,2,4-trimethyl-1,3-oxazolidine-3-carboxylate
• 英文别名: (R)-N-(tert-butoxycarbonyl)-4-hydroxymethyl-2,2,4-trimethyl-3-oxazolidine；(R)-N-(tert-butoxycarbonyl)-4-hydroxymethyl-2,2,4-trimethyloxazolidine
• CAS: 219567-09-6
• 化学式: C₁₂H₂₃NO₄
• 分子量: 245.319
• InChiKey: DSDFDRQZKAXMEL-GFCCVEGCSA-N

物化性质

• 熔点：
  59-60 °C
• 沸点：
  318.6±27.0 °C(Predicted)
• 密度：
  1.051±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (4R)-4-(hydroxymethyl)-2,2,4-trimethyl-1,3-oxazolidine-3-carboxylate 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以96%的产率得到(S)-N-tert-butoxycarbonyl-N,O-isopropylidene-α-methylserinal
  参考文献：
  名称：

  （S）-和（R）-N-Boc-N，O-异亚丙基-α-甲基丝氨酸的制备及合成应用：（S）-和（R）-2-氨基-2-甲基丁酸（Iva）的不对称合成）。

  摘要：

  该报告描述了从（R）-2-甲基缩水甘油5开始的（S）-和（R）-N-Boc-α-甲基丝氨酸丙酮化物（3和4）的高效便捷合成方法。 （S）-和（R）-异缬氨酸（Iva）的合成也证明了在α-甲基氨基酸的不对称合成中这些化合物作为有价值的手性结构单元（6和7）。

  DOI：

  10.1021/jo990957o
• 作为产物：
  描述：

  (1,3-二羟基-2-甲基-2-丙基)(2-甲基-2-丙基)氨基甲酸 在 三氟化硼乙醚 、 CHIRAZYME L-2,carrier-fixed C₃, Iyo 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲基叔丁基醚 、 水 为溶剂， 反应 2.83h， 生成 tert-butyl (4R)-4-(hydroxymethyl)-2,2,4-trimethyl-1,3-oxazolidine-3-carboxylate
  参考文献：
  名称：

  Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P1 agonists

  摘要：

  We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats.

  DOI：

  10.1016/j.bmc.2014.05.035

文献信息

• Preparation and Synthetic Applications of (<i>S</i>)- and (<i>R</i>)-<i>N</i>-Boc-<i>N,O</i>-isopropylidene-α-methylserinals:  Asymmetric Synthesis of (<i>S</i>)- and (<i>R</i>)-2-Amino-2-methylbutanoic Acids (Iva)
  作者：Alberto Avenoza、Carlos Cativiela、Francisco Corzana、Jesús M. Peregrina、María M. Zurbano

  DOI：10.1021/jo990957o

  日期：1999.10.1

  describes an efficient and convenient large-scale synthesis procedure for (S)- and (R)-N-Boc-alpha-methylserinal acetonides (3 and 4) starting from (R)-2-methylglycidol 5. The application of both of these compounds as valuable chiral building blocks in the asymmetric synthesis of alpha-methylamino acids is also demonstrated by the synthesis of (S)- and (R)-isovalines (Iva) (6 and 7).

  该报告描述了从（R）-2-甲基缩水甘油5开始的（S）-和（R）-N-Boc-α-甲基丝氨酸丙酮化物（3和4）的高效便捷合成方法。 （S）-和（R）-异缬氨酸（Iva）的合成也证明了在α-甲基氨基酸的不对称合成中这些化合物作为有价值的手性结构单元（6和7）。
• Synthesis of (S)-N-tert-butoxycarbonyl-N,O-isopropylidene-α-methylserinal: A potential building block for the asymmetric synthesis of non-natural amino acids
  作者：Myriam Alías、Carlos Cativiela、María D. Díaz-de-Villegas、JoséA. Gálvez、Yolanda Lapeña

  DOI：10.1016/s0040-4020(98)00937-5

  日期：1998.12

  The title compound (S)-alpha-methylserinal acetonide has been efficiently prepared from (S)-alpha-methylserine, which is readily available in enantiomerically pure form by Curtius rearrangement of alpha,alpha-dialkyl 2-cyanoesters obtained by diastereoselective alkylation of (1S,2R,4R)-10-dicyclohexylsulfamoylisobornyl 2-cyanopropanoate using methoxymethyl iodide or paraformaldehyde as electrophiles by an extension of our recently developed methodology for the synthesis of alpha,alpha-dialkylamino acids, (C) 1998 Elsevier Science Ltd. All rights reserved.
• Enantioselective synthesis of (S)- and (R)-α-methylserines: application to the synthesis of (S)- and (R)-N-Boc-N,O-isopropylidene-α-methylserinals
  作者：Alberto Avenoza、Carlos Cativiela、Francisco Corzana、Jesús M. Peregrina、David Sucunza、Marı́a M. Zurbano

  DOI：10.1016/s0957-4166(01)00159-8

  日期：2001.4

  This report describes the synthesis of enantiomerically pure (S)- and (R)-alpha -methylserines on a multigram scale, starting from the Weinreb amide of 2-methyl-2-propenoic acid and using a stereodivergent synthetic route that involves a Sharpless asymmetric dihydroxylation reaction. As a synthetic application of these quaternary alpha -amino acids, they were used as starting materials in the synthesis of the well-known valuable homochiral (S)- and (R)-N-Boc-N,O-isopropylidene-alpha -methylserinal building blocks. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Enzymatic desymmetrization of 2-amino-2-methyl-1,3-propanediol: asymmetric synthesis of (S)-N-Boc-N,O-isopropylidene-α-methylserinal and (4R)-methyl-4-[2-(thiophen-2-yl)ethyl]oxazolidin-2-one
  作者：Takashi Tsuji、Yukiko Iio、Toshiyasu Takemoto、Takahide Nishi

  DOI：10.1016/j.tetasy.2005.07.037

  日期：2005.10

  We report herein, the novel enzymatic desymmetrization of 2-tert-butoxycarbonylamino-2-methyl-1,3-propanediol 1. This method makes it possible to prepare (S)-N-Boc-N,O-isopropylidene-alpha-methylserinal 3, which is a chiral building block for the synthesis of a variety of a-substituted alanine derivatives. Moreover, optically active (4R)-methyl-4-[2-(thiophen-2-yl)ethyl]oxazolidin-2-one 4. one of the key intermediates in the synthesis of a novel immunosuppressant, has been prepared by this methodology. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P1 agonists
  作者：Takashi Tsuji、Keisuke Suzuki、Tsuyoshi Nakamura、Taiji Goto、Yukiko Sekiguchi、Takuya Ikeda、Takeshi Fukuda、Toshiyasu Takemoto、Yumiko Mizuno、Takako Kimura、Yumi Kawase、Futoshi Nara、Takashi Kagari、Takaichi Shimozato、Chizuko Yahara、Shinichi Inaba、Tomohiro Honda、Takashi Izumi、Masakazu Tamura、Takahide Nishi

  DOI：10.1016/j.bmc.2014.05.035

  日期：2014.8

  We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats.