(S)-2-[3-(tert-butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl]oxazole-4-carboxylic acid | 890403-75-5

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-2-[3-(tert-butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl]oxazole-4-carboxylic acid
• 英文别名: L2H2-6OTD intermediate-2；2-[(4S)-2,2-dimethyl-3-[(2-methylpropan-2-yl)oxycarbonyl]-1,3-oxazolidin-4-yl]-1,3-oxazole-4-carboxylic acid
• CAS: 890403-75-5
• 化学式: C₁₄H₂₀N₂O₆
• 分子量: 312.323
• InChiKey: ROGULVVSLYGJPQ-VIFPVBQESA-N

物化性质

• 熔点：
  140 °C(Solvent: Ethyl acetate)
• 沸点：
  453.467±45.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.254±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-2-[3-(tert-butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl]oxazole-4-carboxylic acid 在 4-二甲氨基吡啶 、 palladium on activated charcoal 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 二乙胺基三氟化硫 、 4 A molecular sieve 、 叠氮磷酸二苯酯 、 氢气 、 1-羟基苯并三唑 、 甲基磺酰氯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 91.0h， 生成 (12Z,22Z,32Z,72Z,82Z,92Z,12R)-6-(bromomethyl)-12-((tert-butylthio)methyl)-6-methoxy-15,25-dimethyl-5,11-diaza-1(2,4),2,3,7,8,9(4,2)-hexaoxazolacyclododecaphane-4,10-dione
  参考文献：
  名称：

  Total Synthesis of (R)-Telomestatin

  摘要：

  We have achieved a total synthesis of telomestatin, and its absolute configuration was determined to be (R). Coupling of cysteine-containing trisoxazole amine and serine-containing trisoxazole carboxylic acid, followed by macrocyclization, provided a 24-membered diamide. The seventh oxazole ring was formed by a Shin's procedure via dehydroamide. Cyclodehydration of a modified (R)-cysteine-(S-Bu-t) moiety using Kelly's method (PPh3(O)-Tf2O) with anisole furnished (R)-telomestatin, whose CD spectrum was in good agreement with that of the natural product.

  DOI：

  10.1021/ol061793i
• 作为产物：
  描述：

  (S)-(-)-3-BOC-4-甲氧羰基-2,2-二甲基-1,3-恶唑烷 在 lithium hydroxide 、 三氯溴甲烷 、 二乙胺基三氟化硫 、 1-羟基苯并三唑 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 44.0h， 生成 (S)-2-[3-(tert-butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl]oxazole-4-carboxylic acid
  参考文献：
  名称：

  与新型端粒酶抑制剂 Telomestatin 及其类似物的合成相关的双功能化三异恶唑衍生物的有效构建

  摘要：

  由 L-丝氨酸开发了一种与 telomestatin 相关的适当功能化的三异恶唑衍生物的有效构建，其涉及三个连续的恶唑啉环化-氧化步骤，在 11% 的线性序列中的总产率 12 个步骤。

  DOI：

  10.1055/s-2006-926415

文献信息

• Synthesis of Heptaoxazole Macrocyclic Analogues of Telomestatin and Evaluation of Their Telomerase Inhibitory Activities
  作者：Kazuaki Shibata、Masahito Yoshida、Takashi Takahashi、Motoki Takagi、Kazuo Shin-ya、Takayuki Doi

  DOI：10.1246/bcsj.20130198

  日期：2013.12.15

  We have demonstrated various synthetic routes to heptaoxazole macrocyclic analogues of telomestatin and evaluated their inhibitory activities against telomerase. We synthesized three heptaoxazole macrocycles consisting of different numbers of methyloxazole moieties and another heptaoxazole analogue with a bromooxazole moiety instead of one of the two methyloxazole moieties found in the structure of telomestatin. The bromooxazole analogue underwent Suzuki–Miyaura coupling leading to six analogues having aromatic substituents on the oxazole moiety. The substituents on the oxazole moiety in the heptaoxazole macrocycles, which include a methyl group, a bromine atom, and aromatic substituents, did not affect the inhibitory activity of the overall molecule. In addition, three amine-linked analogues were synthesized by modification of the S-tert-butyl group in the bromooxazole analogue with amine-linked α-bromoacetamides. Notably, one of the amine-linked heptaoxazole analogues exhibited almost the same inhibitory activity as telomestatin.

  我们展示了端粒酶七恶唑大环类似物的各种合成路线，并评估了它们对端粒酶的抑制活性。我们合成了三种由不同数量的甲基恶唑分子组成的庚恶唑大环，以及另一种庚恶唑类似物，其中溴恶唑分子取代了端粒丝肽结构中的两个甲基恶唑分子之一。溴恶唑类似物经过铃木-宫拉偶联反应，产生了六种在恶唑分子上具有芳香取代基的类似物。七恶唑大环中恶唑分子上的取代基（包括一个甲基、一个溴原子和芳香取代基）并不影响整个分子的抑制活性。此外，通过用胺连α-溴乙酰胺修饰溴恶唑类似物中的 S-叔丁基，合成了三种胺连类似物。值得注意的是，其中一种胺联七恶唑类似物的抑制活性几乎与端马司他丁相同。
• Efficient Construction of the Carbon Skeleton of the Novel Polyoxazole-Based Cyclopeptide IB-01211 via a Biomimetic Macrocyclisation
  作者：Shital Chattopadhyay、Sovan Singha

  DOI：10.1055/s-0029-1219180

  日期：2010.3

  An efficient construction of the entire carbon skeleton of the novel polyoxazole-based natural product IB-01211 was developed which featured a biomimetic macrocyclisation of an ω-amino acid tethered through two bisoxazole units as the key step.

  开发了一种基于聚恶唑的新型天然产物 IB-01211 的整个碳骨架的有效构建，其特征是通过两个双恶唑单元连接的 ω-氨基酸的仿生大环化作为关键步骤。
• Convergent synthesis of a 24-membered macrocyclic hexaoxazole derivative related to the novel telomerase inhibitor telomestatin
  作者：Shital K. Chattopadhyay、Suman Biswas

  DOI：10.1016/j.tetlet.2006.09.014

  日期：2006.11

  An efficient construction of a 24-membered macrocyclic hexaoxazole derivative pertinent to the synthesis of analogues of the important natural product telomestatin was developed, which featured a convergent union of two trisoxazole units.

  开发了与重要的天然产物端粒他汀类似物的合成有关的24元大环六恶唑衍生物的有效构建，其特征是两个三恶唑单元的会聚结合。
• Efficient Construction of a Doubly Functionalized Trisoxazole Derivative Relevant­ to the Synthesis of the Novel Telomerase Inhibitor Telomestatin and its Analogues
  作者：Shital Chattopadhyay、Suman Biswas、Benoy Pal

  DOI：10.1055/s-2006-926415

  日期：2006.4

  An efficient construction of a suitably functionalized trisoxazole derivative related to telomestatin was developed from L-serine, which involved three sequential oxazoline cyclization-oxidation steps in an overall yield of 11% in a linear sequence of twelve steps.

  由 L-丝氨酸开发了一种与 telomestatin 相关的适当功能化的三异恶唑衍生物的有效构建，其涉及三个连续的恶唑啉环化-氧化步骤，在 11% 的线性序列中的总产率 12 个步骤。
• Total Synthesis of (<i>R</i>)-Telomestatin
  作者：Takayuki Doi、Masahito Yoshida、Kazuo Shin-ya、Takashi Takahashi

  DOI：10.1021/ol061793i

  日期：2006.8.1

  We have achieved a total synthesis of telomestatin, and its absolute configuration was determined to be (R). Coupling of cysteine-containing trisoxazole amine and serine-containing trisoxazole carboxylic acid, followed by macrocyclization, provided a 24-membered diamide. The seventh oxazole ring was formed by a Shin's procedure via dehydroamide. Cyclodehydration of a modified (R)-cysteine-(S-Bu-t) moiety using Kelly's method (PPh3(O)-Tf2O) with anisole furnished (R)-telomestatin, whose CD spectrum was in good agreement with that of the natural product.