(4R,5S)-5-(hydroxymethyl)-4-methyldihydrofuran-2(3H)-one | 81474-43-3

• 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,5S)-5-(hydroxymethyl)-4-methyldihydrofuran-2(3H)-one
• 英文别名: (4R,5S)-5-(hydroxymethyl)-4-methyloxolan-2-one
• CAS: 81474-43-3
• 化学式: C₆H₁₀O₃
• 分子量: 130.144
• InChiKey: FBTOCHKZAQZWSO-RFZPGFLSSA-N

物化性质

• 沸点：
  287.9±13.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R,5S)-5-(hydroxymethyl)-4-methyldihydrofuran-2(3H)-one 在 sodium azide 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 (4S,5S)-5-azidomethyl-4-methyl-4,5-dihydro-2(3H)-furanone
  参考文献：
  名称：

  通过 CoIII(salen) 催化的 (±)-methyl-3-(oxiran-2-yl)butanoate 的两个立体中心水解动力学拆分合成 (+)-tofacitinib 的关键中间体

  摘要：

  摘要 从现成的巴豆醇中获得了高光学纯度 (98% ee) 的对映体纯哌啶，这是合成 (+)-tofacitinib 的关键中间体。所涉及的关键步骤是 CoIII(salen)-OAc 催化的 (±)-methyl-3-(oxiran-2-yl)butanoate 的两个立体中心水解动力学拆分。图形概要

  DOI：

  10.1080/00397911.2018.1434204
• 作为产物：
  描述：

  (5S)-5-[(trityloxy)methyl]tetrahydro-2-furanone 在 platinum(IV) oxide 盐酸 、 sodium periodate 、 18-冠醚-6 、 氢气 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 水 、 乙酸乙酯 为溶剂， -78.0~60.0 ℃ 、294.18 kPa 条件下， 反应 103.0h， 生成 (4R,5S)-5-(hydroxymethyl)-4-methyldihydrofuran-2(3H)-one
  参考文献：
  名称：

  Tomioka, Kiyoshi; Sato, Fuminori; Koga, Kenji, Heterocycles, 1982, vol. 17, p. 311 - 316

  摘要：

  DOI：

文献信息

• A general and concise stereodivergent chiral pool approach toward trans-(4S,5R)- and cis-(4R,5R)-5-alkyl-4-methyl-γ-butyrolactones: Syntheses of (+)-trans- and (+)-cis-whisky and cognac lactones from d-(+)-mannitol
  作者：Avrajit Manna、Ipsita Chakraborty、Sandip Chatterjee、Tanurima Bhaumik

  DOI：10.1016/j.carres.2021.108452

  日期：2021.12

  A straightforward synthesis of (+)-trans-(4S,5R)- and (+)-cis-(4R,5R)-whisky lactones starting from d-(+)-mannitol has been reported here in fewer number of efficient steps compared to existing literature processes involving d-mannitol as the chiral pool starting material. Chiron approach directly translated chirality of d-mannitol to one of the two chiral centers in these target molecules. Toward

  从d -(+)-甘露醇开始直接合成 (+)-反式-(4 S ,5 R )- 和 (+)-顺式-(4 R ,5 R )-威士忌内酯的报道较少与涉及d-甘露醇作为手性池起始材料的现有文献方法相比，有效步骤的数量。Chiron 方法直接将d-甘露醇的手性转化为这些靶分子中的两个手性中心之一。为此，立体异构纯的反式和顺式在倒数第二步中形成碘甲基-γ-内酯。这两种作为通用的高级通用中间体也分别转化为 (+)-反式-(4 S ,5 R )- 和 (+)-顺式-(4 R ,5 R )-干邑内酯。据我们所知，迄今为止还没有报道从d-甘露醇开始合成干邑内酯。所有这些内酯都被确定为陈年酒精饮料的关键香气成分。
• Aminosäuren, 15. Mitt.: Synthese enantiomerenreiner DAVA-Derivate (5-Amino-4-hydroxypentansäuren) aus (S)-Glutaminsäure
  作者：Claus Herdeis、Karen Lütsch、Dagmar Waibel

  DOI：10.1002/ardp.19943270108

  日期：——

  Das aus (S)‐Glutaminsäure zugängliche Hydroxymethyllacton 1 wird als TBDPS‐Ether 2 geschützt. Die Alkylierung des Lithiumenolats von 2 liefert die Lactone 3a,b in hohem Diastereomerenüberschuß. Andererseits erhält man durch 1,4‐Addition der Gilman‐Cuprate an 10 und Abspaltung der Schutzgruppe die Alkohole 12a,b. Die Umsetzung der Alkohole 4,12 über die Mesylate 5,13 und die Azide 6,14 liefert nach

  可以从 (S)-谷氨酸获得的羟甲基内酯 1 被保护为 TBDPS 醚 2。2的烯醇锂的烷基化得到高非对映体过量的内酯3a、b。另一方面，将 Gilman 铜酸盐 1,4-加成到 10 并去除保护基团得到醇 12a、b。在 Boc2O 存在下催化氢化后，醇 4、12 通过甲磺酸盐 5、13 和叠氮化物 6、14 的转化，得到 Boc 保护的胺 7,15。用甲醇 HCl 处理得到结晶盐酸盐 8,16，通过开环将其转化为 DAVA 衍生物（δ-氨基戊酸衍生物）9,17。
• Regio-, stereo-, and enantioselective synthesis of cyclobutanols by means of the photoaddition of 1,3-dioxin-4-ones and lipase-catalyzed acetylation
  作者：Masayuki Sato、Hirohide Ohuchi、Yoshito Abe、Chikara Kaneko

  DOI：10.1016/s0957-4166(00)80211-6

  日期：1992.1

  Homochiral cis-2-hydroxymethylcyclobutanols, their all cis 3-methyl, and 4-hydroxymethyl derivatives were synthesized from 1,3-dioxin-4-ones via cyclobutane ring formation by [2+2]photocycloaddition, dioxanone ring cleavage, and reduction, followed by lipase-catalyzed kinetic resolution of the resulted cyclobutanols. The chiral cyclobutanols thus obtained have been converted to the corresponding gamma-lactones which are potential precursors for a series of biologically active compounds.
• Molecular Basis for the Enantio- and Diastereoselectivity of<i>Burkholderia cepacia</i>Lipase toward γ-Butyrolactone Primary Alcohols
  作者：Heesung Eum、Romas J. Kazlauskas、Hyun-Joon Ha

  DOI：10.1002/adsc.201400510

  日期：2014.11.24

  AbstractBurkholderia cepacia lipase (BCL) shows high enantioselectivity toward chiral primary alcohols, but this enantioselectivity is often unpredictable, especially for substrates that contain an oxygen at the stereocenter. For example, BCL resolves β‐substituted‐γ‐acetyloxymethyl‐γ‐butyrolactones (acetates of a chiral primary alcohol) by hydrolysis of the acetate, but the enantioselectivity varies with the nature and orientation of the β‐alkyl substituent. BCL favors the (R)‐primary alcohol when the β‐alkyl substituent is hydrogen (E=30) or trans methyl (E=38), but the (S)‐primary alcohol when it is cis methyl (E=145). To rationalize this unusual selectivity, we used a combination of experiments to show the importance of polar interactions and modeling to reveal differences in orientations of the enantiomers. Removal of either the lactone carbonyl in the substrate or the polar side chains in the enzyme by using a related enzyme without these side chains decreased the enantioselectivity at least four‐fold. Modeling revealed that the slow enantiomers do not bind by exchanging the location of two substituents relative to the fast enantiomer. Instead, three substituents remain in the same region, but the fourth substituent, hydrogen, inverts to a new location, like an umbrella in a strong wind. In this orientation the favored stereoisomers have similar shapes, thus accounting for the unusual stereoselectivity. The ratio of catalytically productive orientations for the fast vs. slow enantiomers in a molecular dynamic simulation correlated (R2=0.82) with the degree of enantioselectivity including the case where the enantioselectivity reversed. Weighting this ratio by the ratio of H‐bonds in the polar interaction to account for different binding strengths improved the correlation with the measured enantioselectivity to R2=0.97. The modeling identifies key interactions responsible for high enantioselectivity in this class of substrates.magnified image
• Lipase PS (<i>Pseudomonas </i><i>cepacia</i>) Mediated Resolution of γ-Substituted γ-((Acetyloxy)methyl)-γ-butyrolactones:  Complete Stereochemical Reversion by Substituents
  作者：Hyun-Joon Ha、Kyung-Noh Yoon、Sang-Youn Lee、Young-Soo Park、Moon-Soo Lim、Yoon-Gil Yim

  DOI：10.1021/jo981184r

  日期：1998.10.1