<4S,3(2R)>-4-benzyl-3-<4-(tert-butoxycarbonyl)-2-methylbutanoyl>-2-oxazolidinone | 136546-79-7

• 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: <4S,3(2R)>-4-benzyl-3-<4-(tert-butoxycarbonyl)-2-methylbutanoyl>-2-oxazolidinone
• 英文别名: (R)-tert-butyl 5-((S)-4-benzyl-2-oxooxazolidin-3-yl)-4-methyl-5-oxopentanoate；(4S,3(2R))-4-benzyl-3-[4-(tert-butoxycarbonyl)-2-methylbutanoyl]-2-oxazolidinone；tert-butyl (4R)-5-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-4-methyl-5-oxopentanoate
• CAS: 136546-79-7
• 化学式: C₂₀H₂₇NO₅
• 分子量: 361.438
• InChiKey: DWAAHHKAGUNCCR-ZBFHGGJFSA-N

物化性质

• 沸点：
  503.1±33.0 °C(Predicted)
• 密度：
  1.155±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  <4S,3(2R)>-4-benzyl-3-<4-(tert-butoxycarbonyl)-2-methylbutanoyl>-2-oxazolidinone 在 palladium on activated charcoal N-甲基吗啉 、 吡啶 、 2,6-二甲基吡啶 、 盐酸 、 nickel(IV) oxide 、 氯化亚砜 、 过氧化氢,锂盐(1:1) 、 四溴化碳 、 二苯基膦叠氮化物 、 氢气 、 三甲基铝 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 溶剂黄146 、 乙酸乙酯 、 乙腈 、 苯 为溶剂， -25.0~25.0 ℃ 、101.33 kPa 条件下， 反应 17.0h， 生成 (2R,3R,4R)-N-[(3R)-3-[4-(diethoxyphosphorylmethyl)-1,3-oxazol-2-yl]butyl]-4-(dimethylamino)-5-methoxy-2,3-bis(triethylsilyloxy)pentanamide
  参考文献：
  名称：

  Asymmetric synthesis of calyculin A. 2. The C26-C37 .gamma.-amino acid fragments

  摘要：

  New chiral imide enolate alkylation, aldol, and Michael addition bond constructions have been employed in the asymmetric synthesis of the C26-C37 portion of calyculin A.

  DOI：

  10.1021/jo00033a010
• 作为产物：
  描述：

  丙烯酸叔丁酯 、 (S)-4-苄基-3-丙酰基-2-噁唑烷酮 在 titanium(IV)isopropoxide 、 四氯化钛 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以78%的产率得到<4S,3(2R)>-4-benzyl-3-<4-(tert-butoxycarbonyl)-2-methylbutanoyl>-2-oxazolidinone
  参考文献：
  名称：

  Stereoselective Synthesis of Rapamycin Fragment To Build a Macrocyclic Toolbox

  摘要：

  A stereoselective synthesis of a rapamycin fragment is developed and further utilized toward building a macrocyclic chemical toolbox. The amino alcohol moiety embedded in the 22-membered macrocyclic ring allowed for the addition of a variation in the chiral side chain. The key reactions leading to the synthesis of the rapamycin-derived pyran fragment include the following: (i) Paterson aldol, (ii) stereoselective β-OH carbonyl reduction, and (iii) regio- and stereoselective intramolecular oxy-Michael reaction. The other piece needed for building the macrocyclic diversity was obtained from the coupling of various amino alcohol moieties with S-pipecolic acid.

  DOI：

  10.1021/ol5034833

文献信息

• Synthesis and Absolute Stereochemical Assignment of (+)-Miyakolide
  作者：David A. Evans、David H. B. Ripin、David P. Halstead、Kevin R. Campos

  DOI：10.1021/ja990789h

  日期：1999.7.1

  The first total synthesis of the marine macrolide miyakolide has been achieved, and its absolute stereochemistry has been determined. The carbon skeleton is assembled in a convergent fashion from three fragments via esterification, [3 + 2] dipolar cycloaddition, and aldol addition. The utility of β-ketoimide aldol reactions in fragment coupling was demonstrated on fully elaborated intermediates. The

  首次实现了海洋大环内酯类的全合成，并确定了其绝对立体化学。碳骨架由三个片段通过酯化、[3 + 2] 偶极环加成和羟醛加成以会聚方式组装。β-酮亚胺醛醇反应在片段偶联中的效用在完全精心设计的中间体上得到了证明。偶联材料被转化为含有 1,3,7-三酮的大环，该大环经历了简单的跨环醛醇反应，然后进行半缩酮化，形成天然产物的氧化萘烷环系统。脱保护得到 ent-miyakolide，其以 6.8% 的总产率和 29 个线性步骤生产。
• [EN] NEW MACROCYCLIC COMPOUNDS AND DERIVATIVES AS EGFR INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS MACROCYCLIQUES ET LEURS DÉRIVÉS UTILISÉS EN TANT QU'INHIBITEURS D'EGFR
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2020260252A1

  公开（公告）日：2020-12-30

  The present invention encompasses compounds of formula (I) wherein the groups R1 to R3, A, B and L and p and q have the meanings given in the claims and specification, their use as inhibitors of mutant EGFR, pharmaceutical compositions which contain compounds of this kind and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

  本发明涵盖了式（I）中的化合物，其中基团R1至R3、A、B和L以及p和q具有声明和规范中给定的含义，它们作为突变EGFR的抑制剂的用途，含有这类化合物的药物组合物以及它们作为药物/医用品的用途，特别是作为治疗和/或预防肿瘤疾病的药物。
• Total synthesis of (+)-calyculin A
  作者：David A. Evans、James R. Gage、James L. Leighton

  DOI：10.1021/ja00050a024

  日期：1992.11

  A convergent asymmetric synthesis of the marine natural product calyculin A has been accomplished through the union of the two subunits comprising the C1-C25 and C26-C37 portions of the molecule. These fragments were constructed utilizing auxiliary-based asymmetric aldol, alkylation, hydroxylation, and Michael reactions to establish 10 of the 15 stereogenic centers, The remaining chirality was incorporated through internal asymmetric induction. Stereoselective Wittig coupling of the two fragments and subsequent deprotection provided synthetic calyculin A. The spectral properties of the synthetic material were in complete agreement with those of the natural material except for the optical rotation which was equal and opposite in sign to that of the natural material. The absolute configuration of (-)-calyculin A has thus been shown to be opposite to that illustrated in structure 1.
• Dimethyl amino[(phenylthio)methyl]malonate: a useful C-3 unit in a mild, direct synthesis of oxazole-4-carboxylates
  作者：Rafael Shapiro

  DOI：10.1021/jo00073a040

  日期：1993.10

  N-Acyl derivatives of the title compound undergo oxidative cyclization upon treatment with N-chlorosuccinimide in DMF to form dimethyl 4,5-dihydro(phenylthio)oxazole-4,4-dicarboxylates 4 which then are decarbomethoxylated with concomitant loss of thiophenoxide to form 2-substituted-4-carbomethoxy-5-unsubstituted oxazoles 1. The mildness and generality of this method has been demonstrated by the synthesis of a variety of examples, including a fragment used for a synthesis of calyculin A.
• Enantioselective Michael reactions. Diastereoselective reactions of chlorotitanium enolates of chiral N-acyloxazolidinones with representative electrophilic olefins
  作者：David A. Evans、Mark T. Bilodeau、Todd C. Somers、Jon Clardy、David Cherry、Yoko Kato

  DOI：10.1021/jo00020a007

  日期：1991.9

  In the present study we wish to report the details of the diastereoselective reactions of titanium enolates derived from N-propionyloxazolidone 1 in inter-and intramolecular Michael reactions with ethyl vinyl ketone, methyl acrylate, and acrylonitrile (eq 1).