(+)-(2R)-2-[2-(tert-butyldiphenylsiloxy)ethyl]-2H-pyran-4(3H)-one | 869336-43-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: (+)-(2R)-2-[2-(tert-butyldiphenylsiloxy)ethyl]-2H-pyran-4(3H)-one
• 英文别名: (2R)-2-[2-[tert-butyl(diphenyl)silyl]oxyethyl]-2,3-dihydropyran-4-one
• CAS: 869336-43-6
• 化学式: C₂₃H₂₈O₃Si
• 分子量: 380.559
• InChiKey: USSGLRNRXNFXNW-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.82
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-(2R)-2-[2-(tert-butyldiphenylsiloxy)ethyl]-2H-pyran-4(3H)-one 在 sodium tetrahydroborate 、 cerium(III) chloride 作用下， 以 甲醇 为溶剂， 生成 (-)-(2R,4S)-2-[2-(tert-butyldiphenylsiloxy)ethyl]-3,4-dihydro-2H-pyran-4-ol
  参考文献：
  名称：

  通过显着的甲醇诱导的动力学螺环化反应立体控制合成螺缩酮

  摘要：

  甲醇诱导的动力学 spiroketalization 反应已被开发用于立体控制的目标和多样性导向的 spiroketals 合成。与现有的螺缩酮合成方法相比，该反应不依赖于热力学产物的稳定性，也不需要氧亲核试剂的轴向攻击。立体异构糖基在 C1 位被烷基化，侧链带有受保护的羟基。醇脱保护后，糖醛被立体选择性环氧化，然后侧链羟基被螺环化，异头碳通过在 -63 摄氏度加入过量的甲醇而发生构型反转。这种螺环化反应似乎是通过甲醇氢键催化进行的，并具有用于形成具有立体异构取代基的五元和六元环。在某些情况下，

  DOI：

  10.1021/ja055033z
• 作为产物：
  描述：

  反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯 、 3-(tert-butyldiphenylsilyloxy)-1-propanal 在 titanium(IV) isopropylate 、 (R)-1,1'-Bi-2-naphthol 、 三氟乙酸 作用下， 以 乙醚 为溶剂， 反应 24.0h， 生成 (-)-(2S)-2-[2-(tert-butyldiphenylsiloxy)ethyl]-2H-pyran-4(3H)-one 、 (+)-(2R)-2-[2-(tert-butyldiphenylsiloxy)ethyl]-2H-pyran-4(3H)-one
  参考文献：
  名称：

  （+）-苯甲唑A的合成研究。（+）-phorboxazole A的高度收敛的第二代全合成。

  摘要：

  [结构：见正文]已经实现了有效的抗肿瘤药（+）-佛洛他唑A（1）的第二代全合成。这种方法的基石包括一个更趋于收敛的策略，其中包括一个完全精巧的C（1-28）大环与一个C（29-46）侧链的后期Stille并集。第二代合成需要24个步骤的最长线性序列，总产率为4.2％。

  DOI：

  10.1021/ol051584i

文献信息

• Total Synthesis of (+)-Phorboxazole A Exploiting the Petasis−Ferrier Rearrangement
  作者：Amos B. Smith、Kevin P. Minbiole、Patrick R. Verhoest、Michael Schelhaas

  DOI：10.1021/ja011604l

  日期：2001.11.1

  convergent, stereocontrolled total synthesis of the potent antiproliferative agent (+)-phorboxazole A (1) has been achieved. Highlights of the synthesis include: modified Petasis-Ferrier rearrangements for assembly of both the C(11-15) and C(22-26) cis-tetrahydropyran rings; extension of the Julia olefination to the synthesis of enol ethers; the design, synthesis, and application of a novel bifunctional

  已经实现了强效抗增殖剂 (+)-phorboxazole A (1) 的高度收敛、立体控制的全合成。合成的亮点包括：用于组装 C(11-15) 和 C(22-26) 顺式四氢吡喃环的改良 Petasis-Ferrier 重排；Julia 烯化扩展到烯醇醚的合成；一种新型双功能恶唑关键的设计、合成与应用；C(28) 三甲基锡烷与 C(29) 恶唑三氟甲磺酸酯的 Stille 偶联。最长的线性序列导致 (+)-phorboxazole A (1) 为 27 步，总产率为 3%。
• Phorboxazole B synthetic studies: construction of C(1–32) and C(33–46) subtargets
  作者：Ian Paterson、Alan Steven、Chris A. Luckhurst

  DOI：10.1039/b407240e

  日期：——

  The convergent syntheses of the C(1–32) and C(33–46) domains of phorboxazole B are described. An iterative cyclocondensation strategy exploited the Jacobsen hetero-Diels–Alder (HDA) reaction as a platform for the synthesis of both the C(5–9) and C(11–15) tetrahydropyran rings. The use of 2-silyloxydiene coupling partners bearing an increasing resemblance to the phorboxazole skeleton was found to lead to a reduction in diastereoselectivity, however, in the case of the C(11–15) ring. The coupling of aldehyde 21 and 2-silyloxydiene 20 by this route provided a C(1–32) fragment which was elaborated to the macrolide core of phorboxazole B. The synthesis of the C(33–46) domain involved a Nozaki–Kishi coupling of aldehyde 31 and vinyl iodide 39. The syntheses of 31 and 39 were highly diastereoselective: an Evans [Cu(Ph-pybox)](SbF6)2-catalysed Mukaiyama aldol reaction formed the cornerstone of the synthesis of 31 whilst a Nagao–Fujita acetate aldol reaction provided a convenient means of installing the sole stereogenic centre of 39.

  报道了phorboxazole B的C(1–32)和C(33–46)区域的汇聚式合成。一种迭代环加成策略利用了Jacobsen的杂Diels–Alder (HDA)反应作为合成C(5–9)和C(11–15)四氢吡喃环的平台。使用越来越类似于phorboxazole骨架的2-硅氧基二烯作为偶联伙伴，发现导致了对映选择性的降低，但在C(11–15)环的情况下。通过这种方法将醛21和2-硅氧基二烯20偶联，得到了C(1–32)片段，进而发展为phorboxazole B的大环内酯核心。C(33–46)区域的合成涉及醛31和乙烯基碘39的Nozaki–Kishi偶联。31和39的合成高度对映选择性：Evans [Cu(Ph-pybox)](SbF6)2催化的Mukaiyama Aldol反应构成了31合成的基础，而Nagao–Fujita乙酸盐Aldol反应为39唯一手性中心的安装提供了一种便捷的方法。
• Phorboxazole Synthetic Studies. 1. Construction of a C(3−19) Subtarget Exploiting an Extension of the Petasis−Ferrier Rearrangement
  作者：Amos B. Smith、Patrick R. Verhoest、Kevin P. Minbiole、John J. Lim

  DOI：10.1021/ol990830l

  日期：1999.9.1

  text] In this, the first of two letters, we outline our overall strategy for the total synthesis of phorboxazoles A (1) and B (2), rare oxazole-containing macrolides possessing extraordinary antimitotic activity, and describe the assembly of a C(3-19) subtarget (-)-5 for the total synthesis of phorboxazole A. The synthesis of (-)-5 was achieved in 15 linear steps (12% overall yield), exploiting a modification

  [公式：参见文字]在此，两个字母的第一个，我们概述了总合成佛波唑A（1）和B（2），具有罕见抗有丝分裂活性的稀有含恶唑大环内酯的总体策略，并描述了组装过程C（3-19）子目标（-）-5的总合成佛波唑A。（-）-5的合成是通过15线性步骤（总产率为12％）实现的，利用了Petasis-进行载体重排以构建C（11-15）顺式四氢吡喃。事实证明，二甲基氯化铝（Me2AlCl）是Petasis-Ferrier重排的首选路易斯酸。
• Synthetic studies directed toward the phorboxazoles: preparation of the C3–C15 bisoxane segment and two stereoisomers
  作者：Patrick B. Greer、William A. Donaldson

  DOI：10.1016/s0040-4020(02)00613-0

  日期：2002.7

  A synthetic approach to the C3-C15 segment of the cytotoxic marine metabolite phorboxazoles is described. This segment consists of a methylene linked bisoxane structure. The first pyran ring was constructed by a Lewis acid catalyzed diene-aldehyde cyclo-condensation. The beta-C-glucoside substitution pattern of this ring was established by a stereoselective allylation. Ozonolysis of vinyl group and enantioselective allylation of the racemic aldehyde generated two separable homoallylic alcohols (-)-22 and (+)-23. The Mosher's esters of each alcohol were determined to be >90% de. Reaction of (-)-22 with acryloyl chloride, followed by ring closing metathesis gave the dihydro-2-pyrone target (-)-5. Mitsunobu inversion of (+)-23 with p-nitrobenzoic acid, hydrolysis, and esterification with acryloyl chloride and ring closing metathesis gave pseudoenantiomeric segment (+)-6. (C) 2002 Published by Elsevier Science Ltd.
• A Second-Generation Total Synthesis of (+)-Phorboxazole A
  作者：Amos B. Smith、Thomas M. Razler、Jeffrey P. Ciavarri、Tomoyasu Hirose、Tomoyasu Ishikawa、Regina M. Meis

  DOI：10.1021/jo7018152

  日期：2008.2.1

  A highly convergent second-generation synthesis of (+)-phorboxazole A has been achieved. Highlights of the synthetic approach include improved Petasis-Ferrier union/rearrangement conditions on a scale to assemble multigram quantities of the C(11-15) and C(22-26) cis-tetrahydropyrans inscribed with the phorboxazole architecture, a convenient method to prepare E- and Z-vinyl bromides from TMS-protected alkynes utilizing radical isomerization of Z-vinylsilanes, and a convergent late-stage Stille union to couple a fully elaborated C(1-28) macrocyclic iodide with a C(29-46) oxazole stannane side chain to establish the complete phorboxazole skeleton. The synthesis, achieved with a longest linear sequence of 24 steps, proceeded in 4.6% overall yield.