(4R,3S)-4,5-dihydroxy-3-(1-methylethyl)pentanoic acid γ-lactone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (4R,3S)-4,5-dihydroxy-3-(1-methylethyl)pentanoic acid γ-lactone
• 英文别名: (3S,4S)-3-isopropyl-4-(hydroxymethyl)butan-4-olide；D-threo-Pentonic acid, 2,3-dideoxy-3-(1-methylethyl)-, gamma-lactone (9CI)；(4S,5S)-5-(hydroxymethyl)-4-propan-2-yloxolan-2-one
• 化学式: C₈H₁₄O₃
• 分子量: 158.197
• InChiKey: ZJLRHKUWYSGGNX-NKWVEPMBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  ethyl (Z)-3-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)acrylate 在 盐酸 、 偶氮二异丁腈 、 四丁基氟化铵 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 甲醇 、 苯 为溶剂， 反应 5.5h， 生成 (4R,3S)-4,5-dihydroxy-3-(1-methylethyl)pentanoic acid γ-lactone
  参考文献：
  名称：

  Syn-Selective Michael Addition of Nitromethane Derivatives to Enoates Derived from (R)-(+)-Glyceraldehyde Acetonide

  摘要：

  We report the syn-selective Michael addition of a series of substituted primary and secondary nitromethane derivatives 4a-g to chiral enoates (Z)-2a and (E)-2a in the presence of TBAF . 3H(2)O or DBU. Regardless of the base employed, adducts syn-5a-g were obtained in good de (80-100%) from the reactions of 4a-g with (Z)-2a. However, in the addition to (E)-2a, the syn-diastereoselectivities depended on the structure of the nucleophile (80-90% de for nitromethane (4a), 80% de for phenylnitromethane (4g), 50 and 34% de for the primary nitromethane derivatives 4b and 4d, and 0 and 6% de for the secondary nitromethane derivatives 4e and 4f). A mixture of epimers (2:1/1:1) was obtained at the chiral center bearing the nitro group in 5b and 5d-g. The syn/anti ratio C-3,C-4 is kinetically controlled, while the epimeric ratio at the CNO2 chiral center (C-1') seems to be thermodynamically controlled. Adducts 5a,b,c,g were transformed into the respective cis-beta,gamma-disubstituted gamma-butyrolactones 6a, 7, 9a, and 9e. A mechanistic rationale to explain the observed diastereoselectivities is proposed.

  DOI：

  10.1021/jo960788x

文献信息

• Total Synthesis of Methyl Sarcophytoate, a Marine Natural Biscembranoid
  作者：Takahiro Ichige、Yusuke Okano、Naoki Kanoh、Masaya Nakata

  DOI：10.1021/jo802249k

  日期：2009.1.2

  The total synthesis of methyl sarcophytoate (1), a marine natural biscembranoid, has been achieved by the thermal Diels−Alder reaction between the 14-membered dienophile unit, methyl sarcoate (2), and the 14-membered diene unit 64. Methyl sarcoate (2) was prepared using n-BuLi-Bu2Mg-mediated dithiane coupling, Kosugi−Migita−Stille coupling, and Grubbs ring-closing metathesis. The diene unit 64 was

  十二烷基肌醇二甲酯（1）（一种海洋天然双树皮）的总合成已通过14元亲二烯体单元，十二烷酸甲酯（2）和14元二烯单元64之间的热Diels-Alder反应实现。使用n -BuLi-Bu 2 Mg介导的二噻吩偶联，Kosugi-Migita-Stille偶联和Grubbs闭环复分解反应制备肌氨酸甲酯（2）。使用Sharpless不对称环氧化，Grubbs闭环易位，6-exo-tet环氧化物开环和n -BuLi-Bu 2 Mg介导的Ito-Kodama环化反应制备二烯单元64。2之间的最终Diels-Alder反应和64继续进行高部位，内/外，π-面，和区域选择性。在该反应过程中，在C4位置观察到部分E → Z异构化。
• Diastereoselective Conjugate Addition to Chiralα,β-Unsaturated Carbonyl Systems in Aqueous Media: An Enantioselective Entry toα- andγ-Hydroxy Acids andα-Amino Acids
  作者：Rosa M. Suárez、José Pérez Sestelo、Luis A. Sarandeses

  DOI：10.1002/chem.200304790

  日期：2003.9.5

  induced zinc--copper conjugate addition of iodides to chiral alpha,beta-unsaturated carbonyl systems under aqueous conditions was studied. Alkyl iodides add diastereoselectively to methylenedioxolanone 1 and methyleneoxazolidinone 2 to afford the 1,4-addition products in good yields (38-95 %) and with high diastereomeric excess (44-90 % de). The 1,4-addition to chiral gamma,delta-dioxolanyl-alpha,beta-unsaturated

  研究了在水性条件下超声诱导的碘化物锌-铜共轭加成到手性α，β-不饱和羰基体系上的立体选择性。烷基碘化物非对映选择性地加到亚甲基二氧戊环酮1和亚甲基恶唑烷酮2中，以高收率（38-95％）和高非对映异构体过量（44-90％de）提供1，4-加成产物。向手性γ，δ-二氧杂戊酰基-α，β-不饱和酯3-5加成1，4-也以良好的收率（51-99％）进行。非对映选择性取决于烯烃的几何形状：Z异构体3具有高非对映选择性，而与E异构体4的反应是非对映选择性的。该反应以优异的化学选择性进行，并允许使用带有酯，羟基和氨基的碘化物。从1开始 4-加成产物可以很容易地水解，这种方法为在水性介质中α-和γ-羟基酸和α-氨基酸的对映选择性合成提供了一个新的途径。获得的结果支持Luche提出的自由基机理，并且代表了在水性介质中自由基立体选择性共轭加成的少数例子之一。
• Synthetic studies on biscembranoids: asymmetric total synthesis of methyl sarcoate
  作者：Takahiro Ichige、Satoshi Kamimura、Kazuya Mayumi、Yasuyuki Sakamoto、Shingo Terashita、Eriko Ohteki、Naoki Kanoh、Masaya Nakata

  DOI：10.1016/j.tetlet.2004.12.132

  日期：2005.2

  The asymmetric total synthesis of a marine natural product, methyl sarcoate, has been achieved featuring the asymmetric Michael addition, the dithiane coupling, the Kosugi-Migita-Stille coupling, and the ring-closing metathesis. (C) 2005 Elsevier Ltd. All rights reserved.
• Syn-Selective Michael Addition of Nitromethane Derivatives to Enoates Derived from (<i>R</i>)-(+)-Glyceraldehyde Acetonide
  作者：Jeronimo S. Costa、Ayres G. Dias、Aline L. Anholeto、Mônica D. Monteiro、Vera L. Patrocinio、Paulo R. R. Costa

  DOI：10.1021/jo960788x

  日期：1997.6.13

  We report the syn-selective Michael addition of a series of substituted primary and secondary nitromethane derivatives 4a-g to chiral enoates (Z)-2a and (E)-2a in the presence of TBAF . 3H(2)O or DBU. Regardless of the base employed, adducts syn-5a-g were obtained in good de (80-100%) from the reactions of 4a-g with (Z)-2a. However, in the addition to (E)-2a, the syn-diastereoselectivities depended on the structure of the nucleophile (80-90% de for nitromethane (4a), 80% de for phenylnitromethane (4g), 50 and 34% de for the primary nitromethane derivatives 4b and 4d, and 0 and 6% de for the secondary nitromethane derivatives 4e and 4f). A mixture of epimers (2:1/1:1) was obtained at the chiral center bearing the nitro group in 5b and 5d-g. The syn/anti ratio C-3,C-4 is kinetically controlled, while the epimeric ratio at the CNO2 chiral center (C-1') seems to be thermodynamically controlled. Adducts 5a,b,c,g were transformed into the respective cis-beta,gamma-disubstituted gamma-butyrolactones 6a, 7, 9a, and 9e. A mechanistic rationale to explain the observed diastereoselectivities is proposed.