1,1-dimethylethyl (4R-trans)-4-hydroxymethyl-2,2,5-trimethyl-3-oxazolidine carboxylate | 157336-86-2

• 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: 1,1-dimethylethyl (4R-trans)-4-hydroxymethyl-2,2,5-trimethyl-3-oxazolidine carboxylate
• 英文别名: tert-butyl (4R,5R)-4-hydroxymethyl-2,2,5-trimethyloxazolidine-3-carboxylate；Tert-butyl (4R,5R)-4-(hydroxymethyl)-2,2,5-trimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 157336-86-2
• 化学式: C₁₂H₂₃NO₄
• mdl: MFCD09863822
• 分子量: 245.319
• InChiKey: JVGUACRTSCOTQB-RKDXNWHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.916
• 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：

  1,1-dimethylethyl (4R-trans)-4-hydroxymethyl-2,2,5-trimethyl-3-oxazolidine carboxylate 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 反应 0.58h， 生成 methyl (2E,4R,5R)-4-<(tert-butoxycarbonyl)amino>-5-hydroxy-2-hexenoate acetonide
  参考文献：
  名称：

  Reductive cleavage reaction of .gamma.-functionalized .alpha.,.beta.-unsaturated esters and halomethyls mediated with magnesium in methanol

  摘要：

  Reductive cleavage of various types of C-O and C-N bonds tethered to alpha,beta-unsaturated esters and halomethyls was mediated with magnesium in methanol, which provided a facile method for the synthesis of delta-hydroxy or delta-amino beta,gamma-unsaturated esters and allylic alcohols. Regardless of the geometry (E or Z) of the alpha,beta-unsaturated esters, 1a-b, 5a-c, 11, 13, and 23, the cleavage product obtained was exclusively the E isomer of the corresponding deconjugated hydroxy and amino esters. The steric bias and ring strain of 15, 17, and 21 gave rise to a product mixture of E and Z isomers.

  DOI：

  10.1021/jo00058a038
• 作为产物：
  描述：

  3-(tert-butyl) 4-methyl (4S,5R)-2,2,5-trimethyloxazolidine-3,4-dicarboxylate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 1,1-dimethylethyl (4R-trans)-4-hydroxymethyl-2,2,5-trimethyl-3-oxazolidine carboxylate
  参考文献：
  名称：

  色分子与 MBH 碳酸酯的对映选择性 [3+2]-环加成的合成和计算研究

  摘要：

  通过 3-氰基色酮与 Morita-Baylis-Hillman 碳酸盐的 [3+2]-环加成，开发了高效且直接地获得对映体富集的五元环稠合色酮。以高产率和高 ee 和 dr （ ≤97% 产率、97% ee 和 >20:1 dr）获得了具有三个连续四元和叔立体碳中心的密集官能化手性环戊二烯色酮。此外，已经进行了密度泛函理论计算以研究反应的机理以及区域和非对映选择性。

  DOI：

  10.1021/acs.orglett.2c01922

文献信息

• Structural Requirements for the Antiproliferative Activity of Pre-mRNA Splicing Inhibitor FR901464
  作者：Sami Osman、Brian J. Albert、Yanping Wang、Miaosheng Li、Nancy L. Czaicki、Kazunori Koide

  DOI：10.1002/chem.201002402

  日期：2011.1.17

  inessential, leading to a new potent analogue. Additionally, partially based on in vivo data, we synthesized and evaluated potentially more metabolically stable analogues for their antiproliferative activity. These structural insights into FR901464 may contribute to the simplification of the natural product for further drug development.

  FR901464 是一种从细菌来源分离的天然产物，可激活报告基因、抑制前 mRNA 剪接并显示抗肿瘤活性。我们之前报道了通过 FR901464 的全合成开发了更有效的类似物美亚霉素。在此，我们报告了 FR901464 的详细结构-活性关系，揭示了环氧化物、四氢吡喃环中的碳原子、Z侧链、1,3-二烯部分、C4-羟基和C2''-羰基的几何结构。重要的是，发现乙酰基取代基的甲基是无关紧要的，从而产生了一种新的有效类似物。此外，部分基于体内数据，我们合成并评估了潜在的代谢稳定类似物的抗增殖活性。这些对 FR901464 的结构见解可能有助于简化天然产物以进行进一步的药物开发。
• [EN] PYRIDAZINONES AS PARP7 INHIBITORS<br/>[FR] PYRIDAZINONES UTILISÉES EN TANT QU'INHIBITEURS DE PARP7
  申请人：RIBON THERAPEUTICS INC

  公开号：WO2021087025A1

  公开（公告）日：2021-05-06

  The present invention relates to pyridazinones and related compounds which are inhibitors of PARP7 and are useful in the treatment of cancer.

  本发明涉及吡啶并嗪酮和相关化合物，其为PARP7的抑制剂，可用于癌症治疗。
• From the Feist-Bénary Reaction to Organocatalytic Domino Michael-Alkylation Reactions: Asymmetric Synthesis of 3(2 H)-Furanones
  作者：Xiaowei Dou、Xiaoyu Han、Yixin Lu

  DOI：10.1002/chem.201102796

  日期：2012.1.2

  It all adds up! A modified Feist–Bénary reaction employing a domino Michael–alkylation sequence was designed for the enantioselective synthesis of 3(2 H)‐furanones. L‐Threonine‐derived tertiary amine/thiourea catalysts were prepared for the first time; such catalysts promoted the designed domino Michael–alkylation reactions in a highly enantioselective manner (see scheme).

  这一切加起来！使用多米诺骨牌迈克尔-烷基化序列的改进的Feist-Bénary反应设计用于3（2 H）-呋喃酮的对映选择性合成 。首次制备了L-苏氨酸衍生的叔胺/硫脲催化剂；这类催化剂以高度对映选择性的方式促进了设计的多米诺骨牌迈克尔-烷基化反应（参见方案）。
• An improved method for culturing Streptomyces sahachiroi: Biosynthetic origin of the enol fragment of azinomycin B
  作者：Gilbert T. Kelly、Vasudha Sharma、Coran M.H. Watanabe

  DOI：10.1016/j.bioorg.2007.08.002

  日期：2008.2

  Azinomycin B is an environmental DNA crosslinking agent produced by the soil microorganism Streptomyces sahachiroi. While the agent displays potent cytotoxic activities against leukemic cell lines and animal mouse models, the lack of a consistent supply of the natural product has hampered detailed biological investigations on the compound, including its mode of action and biosynthesis. We report here a significant methodological improvement in the culturing of the bacterium, which allows reliable and steady production of the natural product in good yields. The key experimental step involves the culturing of the strain on dehydrated plates, followed by the generation of a two-stage starter culture and subsequent fermentation of the strain under nutrient-starved conditions. We illustrate use of this culture system by investigating the formation of the enol fragment of the molecule in isotopic labeling experiments with threonine and several advanced precursors (beta-ketoamino acid 3, beta-hydroxyamino aldehyde 4, and beta-ketoaminoaldehyde 5). The results unequivocally show that threonine is the most advanced precursor accepted by the NRPS (non-ribosomal peptidyl synthetase) machinery for final processing and construction of the enol moiety of the natural product. (C) 2007 Elsevier Inc. All rights reserved.
• A Straightforward Synthesis of N-Boc-L-serinal and N-Boc-L-threoninal Acetonides
  作者：Patrick Meffre、Philippe Durand、Eric Branquet、Fran°Cois Le Goffic

  DOI：10.1080/00397919408010228

  日期：1994.8

  An improved procedure for the synthesis of optically active N-tertbutoxycarbonyl L-serinal acetonide and threoninal analogue from ester precursors is described.