tert-butyl N-[(1S,2R)-2-[(2R)-1-[tert-butyl(diphenyl)silyl]oxypropan-2-yl]-1-prop-2-enylcyclopentyl]carbamate | 250595-69-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: tert-butyl N-[(1S,2R)-2-[(2R)-1-[tert-butyl(diphenyl)silyl]oxypropan-2-yl]-1-prop-2-enylcyclopentyl]carbamate
• CAS: 250595-69-8
• 化学式: C₃₂H₄₇NO₃Si
• 分子量: 521.816
• InChiKey: SKEGCCURJOZUIC-AAMSNGAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.84
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(1S,2R)-2-[(2R)-1-[tert-butyl(diphenyl)silyl]oxypropan-2-yl]-1-prop-2-enylcyclopentyl]carbamate 在 9-borabicyclo[3.3.1]nonane dimer 、 potassium carbonate 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 tert-butyl (2'R,6S,9aR)-2'-[(2R)-1-[tert-butyl(diphenyl)silyl]oxypropan-2-yl]-2-oxospiro[3,4,7,8,9,9a-hexahydro-1H-quinolizine-6,1'-cyclopentane]-3-carboxylate
  参考文献：
  名称：

  Total Synthesis of (+)-Halichlorine: An Inhibitor of VCAM-1 Expression

  摘要：

  The diastereoselective addition of the highly functionalized organozinc compound 1 to the aldehyde 2 in the presence of the chiral amino alcohol 3 (-->4) is a key step in the first total synthesis of (+)-halichlorine. A series of protections/deprotections and a macrolaconization complete the synthesis. Halichlorine selectively inhibits the expression of the cell adhesion molecule VCAM-1. TBS=tert-butyldimethylsilyl.

  DOI：

  10.1002/(sici)1521-3773(19991203)38:23<3542::aid-anie3542>3.0.co;2-i
• 作为产物：
  描述：

  (R)-2-((1R,2S)-2-Allyl-2-tert-butoxycarbonylamino-cyclopentyl)-propionic acid 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 tert-butyl N-[(1S,2R)-2-[(2R)-1-[tert-butyl(diphenyl)silyl]oxypropan-2-yl]-1-prop-2-enylcyclopentyl]carbamate
  参考文献：
  名称：

  Total Synthesis of (+)-Halichlorine: An Inhibitor of VCAM-1 Expression

  摘要：

  The diastereoselective addition of the highly functionalized organozinc compound 1 to the aldehyde 2 in the presence of the chiral amino alcohol 3 (-->4) is a key step in the first total synthesis of (+)-halichlorine. A series of protections/deprotections and a macrolaconization complete the synthesis. Halichlorine selectively inhibits the expression of the cell adhesion molecule VCAM-1. TBS=tert-butyldimethylsilyl.

  DOI：

  10.1002/(sici)1521-3773(19991203)38:23<3542::aid-anie3542>3.0.co;2-i

文献信息

• On the Conformations of Halichlorine and the Pinnaic Acids: Nitrogen Inversion as a Possible Determinant of Biological Profile
  作者：Dirk Trauner、David G. Churchill、Samuel J. Danishefsky

  DOI：10.1002/1522-2675(20000906)83:9<2344::aid-hlca2344>3.0.co;2-2

  日期：2000.9.6

  intermediates 3 and 4, containing the spiroquinolizidine core, exhibit the transoid conformation, while the macrolactone-containing halichlorine has the cisoid conformation. We conclude that constraints imposed upon closure of the macrolactone ring force adoption of the cisoid conformation. The major conformational reorganization upon macrolactonization has implications for the design of pharmacophors

  尽管含有喹啉环系统的海洋生物碱卤氯 (1) 和海松酸 2 表现出相当大的结构同源性，但它们作用于不同的生物靶标（分别为 VCAM-1 和 cPLA2）。Quinolizidines 可以作为顺式或反式逆变器存在。在最近报道的(+)-卤代氯的全合成中，通过NMR确定含有螺喹啉核心的高级中间体3和4表现出反式构象，而含有大环内酯的卤代氯具有顺式构象。我们得出结论，对封闭大环内酯环施加的约束迫使采用顺式构象。
• Studies towards the total synthesis of halichlorine: asymmetric synthesis of the spiroquinolizidine subunit
  作者：Dirk Trauner、Samuel J Danishefsky

  DOI：10.1016/s0040-4039(99)01170-3

  日期：1999.9

  The C1-C15 spiroquinolizidine subunit (cf. 2) of the marine natural product halichlorine (1) was prepared in 12 steps starting from the known 'Meyers-lactam' 5. The synthesis involves a B-alkyl-Suzuki coupling followed by a highly stereoselective intramolecular Michael addition and an intramolecular Mannich ring closure. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Concise Stereoselective Routes to Advanced Intermediates Related to Natural and Unnatural Pinnaic Acid This work was supported by the National Institutes of Health (Grant Numbers: CA28824). Postdoctoral Fellowship support is gratefully acknowledged by M.W.C. (U.S. Army BCRP, DAMD17-98-1-8154), M.F.H. (5T32 CA62948-05), and D.T. (Schering Research Foundation, Berlin). We thank Dr. George Sukenick of the MSKCC NMR Core Facility for NMR and mass spectral analyses.
  作者：Matthew W. Carson、Guncheol Kim、Martin F. Hentemann、Dirk Trauner、Samuel J. Danishefsky

  DOI：10.1002/1521-3773(20011203)40:23<4450::aid-anie4450>3.0.co;2-m

  日期：2001.12.3
• Total Synthesis of (+)-Halichlorine: An Inhibitor of VCAM-1 Expression
  作者：Dirk Trauner、Jacob B. Schwarz、Samuel J. Danishefsky

  DOI：10.1002/(sici)1521-3773(19991203)38:23<3542::aid-anie3542>3.0.co;2-i

  日期：——

  The diastereoselective addition of the highly functionalized organozinc compound 1 to the aldehyde 2 in the presence of the chiral amino alcohol 3 (-->4) is a key step in the first total synthesis of (+)-halichlorine. A series of protections/deprotections and a macrolaconization complete the synthesis. Halichlorine selectively inhibits the expression of the cell adhesion molecule VCAM-1. TBS=tert-butyldimethylsilyl.