(+)-papulacandin D | 61036-49-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 糖脂
• 英文名称: (+)-papulacandin D
• 英文别名: papulacandin D；[(3S,3'R,4'S,5'R,6'R)-3',4,5',6-tetrahydroxy-6'-(hydroxymethyl)spiro[1H-2-benzofuran-3,2'-oxane]-4'-yl] (2E,4E,7S,8E,10E,14S)-7-hydroxy-8,14-dimethylhexadeca-2,4,8,10-tetraenoate
• CAS: 61036-49-5
• 化学式: C₃₁H₄₂O₁₀
• 分子量: 574.668
• InChiKey: XKSZJTQIZHUMGA-HPZFVNCBSA-N

物化性质

• 熔点：
  126-128 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  825.5±65.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  166
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3,5-二羟基苯甲酸甲酯 在 咪唑 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 、 Amberlite IR-120 、 三(二甲氨基)锍二氟三甲基硅酸 、 叔丁基锂 作用下， 以 四氢呋喃 、 四氯化碳 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 83.0h， 生成 (+)-papulacandin D
  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

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 of Papulacandin D
  作者：Scott E. Denmark、Christopher S. Regens、Tetsuya Kobayashi

  DOI：10.1021/ja070071z

  日期：2007.3.1

  A total synthesis of the antifungal agent papulacandin D is reported. The molecule is representative of a large class of C-aryl glycosides that exhibit significant antifungal activity. The synthetic strategy bifurcates the molecule into two nearly equal subunits, the arylglycoside and 18-carbon fatty acid side chain. The key strategic transformations are (1) the palladium catalyzed, organosilanolate-based cross-coupling of a protected glucal silanol and (2) a catalytic enantioselective allylation of a dienal using allyltrichlorosilane. The synthesis was accomplished in 31 steps overall from commercial starting materials to afford over 50 mg of the natural product.
• Total synthesis of (+)-papulacandin D
  作者：Scott E. Denmark、Tetsuya Kobayashi、Christopher S. Regens

  DOI：10.1016/j.tet.2010.03.093

  日期：2010.6

  A total synthesis of (+)-papulacandin D has been achieved in 31 steps, in a 9.2% overall yield from commercially available materials. The synthetic strategy divided the molecule into two nearly equal sized subunits, the spirocyclic C-arylglycopyranoside and the polyunsaturated fatty acid side-chain. The C-arylglycopyranoside was prepared in 11 steps in a 30% overall yield from triacetoxyglucal. The fatty acid side-chain was also prepared in 11 steps in a 30% overall yield from geraniol. The key strategic transformations in the synthesis are: (1) a palladium-catalyzed, organosilanolate-based cross-coupling reaction of a dimethylglucal-silanol with an electron-rich and sterically hindered aromatic iodide and (2) a Lewis-base catalyzed, enantioselective allylation reaction of a dienal and allyltrichlorosilane. A critical element in the successful execution of the synthesis was the development of a suitable protecting group strategy that satisfied a number of stringent criteria. (C) 2010 Elsevier Ltd. All rights reserved.
• 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).