2-bromo-3,5-bis<(triisopropylsilyl)oxy>benzyl alcohol | 174464-92-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-bromo-3,5-bis<(triisopropylsilyl)oxy>benzyl alcohol
• 英文别名: 2-Bromo-3,5-Bis[(triisopropylsilyl)oxy]benzyl Alcohol；[2-Bromo-3,5-bis[tri(propan-2-yl)silyloxy]phenyl]methanol
• CAS: 174464-92-7
• 化学式: C₂₅H₄₇BrO₃Si₂
• 分子量: 531.721
• InChiKey: DKPPFKSTIDEGGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.05
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromo-3,5-bis<(triisopropylsilyl)oxy>benzyl alcohol 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 Amberlite IR-120 、 叔丁基锂 作用下， 以 二氯甲烷 为溶剂， 反应 55.5h， 生成 1,1-anhydro-1-C-<6-(hydroxymethyl)-2,4-bis<(triisopropylsilyl)oxy>phenyl>-4,6-O-(tetraisopropyldisiloxane-1,3-diyl)-2-O-<(triethylsilyl)oxy>-β-D-glucopyranose
  参考文献：
  名称：

  Total Synthesis and Structural Elucidation of the Antifungal Agent Papulacandin D

  摘要：

  Condensation of the aryllithium reagents, prepared from the bromides 10 and 11 and tert-butyllithium, with lactone 19 and acid-catalyzed spirocyclization gave the papulacandin spiroketals 14 and 15. Subsequent protection using di-tert-butylsilyl bis(trifluoromethanesulfonate) gave the diols 31 and 30. Isoleucine (37) was converted using a double Wittig reaction sequence and propargylation of the intermediate aldehyde 46 into the alkynol 47. Separation of the C-7 epimers of 47 was achieved using kinetic resolution via Sharpless epoxidation. Both alkynol epimers 53 and 57 were converted into the papulacandin side chain esters 65 and 66 using a hydrozirconation and palladium(0)-catalyzed coupling sequence. Comparisons of Mosher ester derivatives of 65 and 66 with the Mosher ester derivative of the natural papulacandin side chain and further degradation were consistent with the stereochemistry of the natural product being 7S,14S. Esterification of the spiroketals with the mixed anhydride 70 and global deprotection gave papulacandin D (1).

  DOI：

  10.1021/jo951895e
• 作为产物：
  描述：

  3,5-二羟基苯甲酸甲酯 在 咪唑 、 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 作用下， 以 四氯化碳 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-bromo-3,5-bis<(triisopropylsilyl)oxy>benzyl alcohol
  参考文献：
  名称：

  First Construction of a Saricandin Analog Corresponding to Papulacandin D

  摘要：

  首次实现了与papulacandin D相对应的saricandin类似物的全合成，这一成果是通过高度收敛的合成策略实现的。通过pinanyl-9-BBN的不对称还原，设计并大规模制备了易于获得的手性构建块3。化合物3在结构修饰上的适应性以及方法的高度收敛性，体现在通过钯催化的交叉偶联反应将2和3构建出saricandin中的侧链，以及包含三键还原片段C(5-16)和使用Horner-Emmons反应生成双键(C4-C5)的序列中。描述了将螺环单糖苷与saricandin侧链组装的过程。讨论了在用TBAF脱保护后分离最终产物1的实用技术。对化合物1进行了酶活性测试和基于细胞的活性测试，以评估其抗真菌活性。然而，与Traxler报道的papulacandin D活性相比，天然saricandin中存在的半乳糖部分和短脂肪酸似乎对抗真菌活性至关重要。

  DOI：

  10.1055/s-2001-13399

文献信息

• Total synthesis of the antifungal agent papulacandin D
  作者：Anthony G. M. Barrett、Michael Peña、J. Adam Willardsen

  DOI：10.1039/c39950001147

  日期：——

  Condensation of 2,3,4,6-tetra-O-(trimethylsilyl)-D-gluconolactone with tert-butyl[2-lithio-3,5-di-(triisopropylsilyloxy)benzyloxy]dimethylsilane, protection of the resultant spiroketal with di(tert-butyl)silyl di(trifluoromethanesulfonate), selective O-3′-esterification and deprotection gives papulacandin D.

  2,3,4,6-四-O-(三甲基硅基)-D-葡糖醛内酯与叔丁基[2-锂代-3,5-双(三异丙基硅氧基)苯氧基]二甲基硅烷缩合，所得螺缩酮用二(叔丁基)硅基二(三氟甲磺酸)保护，选择性O-3′-酯化和脱保护得到皮刺芹二酮D。
• Total Synthesis and Structural Elucidation of the Antifungal Agent Papulacandin D
  作者：Anthony G. M. Barrett、Michael Peña、J. Adam Willardsen

  DOI：10.1021/jo951895e

  日期：1996.1.1

  Condensation of the aryllithium reagents, prepared from the bromides 10 and 11 and tert-butyllithium, with lactone 19 and acid-catalyzed spirocyclization gave the papulacandin spiroketals 14 and 15. Subsequent protection using di-tert-butylsilyl bis(trifluoromethanesulfonate) gave the diols 31 and 30. Isoleucine (37) was converted using a double Wittig reaction sequence and propargylation of the intermediate aldehyde 46 into the alkynol 47. Separation of the C-7 epimers of 47 was achieved using kinetic resolution via Sharpless epoxidation. Both alkynol epimers 53 and 57 were converted into the papulacandin side chain esters 65 and 66 using a hydrozirconation and palladium(0)-catalyzed coupling sequence. Comparisons of Mosher ester derivatives of 65 and 66 with the Mosher ester derivative of the natural papulacandin side chain and further degradation were consistent with the stereochemistry of the natural product being 7S,14S. Esterification of the spiroketals with the mixed anhydride 70 and global deprotection gave papulacandin D (1).
• First Construction of a Saricandin Analog Corresponding to Papulacandin D
  作者：Chafiq Hamdouchi、Concha Sanchez-Martinez

  DOI：10.1055/s-2001-13399

  日期：——

  The first total synthesis of a saricandin analog corresponding to papulacandin D has been achieved via a highly convergent synthetic strategy. A readily accessible chiral building block 3 was designed and prepared in large scale via an enantioselective reduction with pinanyl-9-BBN. The adaptability of compound 3 toward structural modifications and the highly convergent nature of the approach is illustrated in the construction of the side chain present in saricandin by Pd-catalyzed cross-coupling of 2 and 3 and sequences that include triple bond reduction of fragment C(5-16) and generation of the double bond (C4-C5) using Horner-Emmons reaction. The assembly of the spirocyclic monoglycoside with saricandin side chain is described. A practical technique for isolating the final product 1 after deprotection with TBAF is discussed. Compound 1 was evaluated for its antifungal activity in enzyme assay and cell based assays. However, in contrast the activity reported by Traxler for papulacandin D, the presence of the galactose moiety together with the short fatty acid in natural saricandin seem to be essential for the antifungal activity.

  首次实现了与papulacandin D相对应的saricandin类似物的全合成，这一成果是通过高度收敛的合成策略实现的。通过pinanyl-9-BBN的不对称还原，设计并大规模制备了易于获得的手性构建块3。化合物3在结构修饰上的适应性以及方法的高度收敛性，体现在通过钯催化的交叉偶联反应将2和3构建出saricandin中的侧链，以及包含三键还原片段C(5-16)和使用Horner-Emmons反应生成双键(C4-C5)的序列中。描述了将螺环单糖苷与saricandin侧链组装的过程。讨论了在用TBAF脱保护后分离最终产物1的实用技术。对化合物1进行了酶活性测试和基于细胞的活性测试，以评估其抗真菌活性。然而，与Traxler报道的papulacandin D活性相比，天然saricandin中存在的半乳糖部分和短脂肪酸似乎对抗真菌活性至关重要。