methyl (4R,6S,7R,8S,10S,12E,14R,17S,18R,19S,22S)-3,7,17-trihydroxy-19-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-6,8-dimethoxy-4,10,12,18-tetramethyl-2,15,21-trioxo-14-prop-2-enyl-20-oxa-1-azabicyclo[20.4.0]hexacos-12-ene-3-carboxylate | 133523-40-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: methyl (4R,6S,7R,8S,10S,12E,14R,17S,18R,19S,22S)-3,7,17-trihydroxy-19-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-6,8-dimethoxy-4,10,12,18-tetramethyl-2,15,21-trioxo-14-prop-2-enyl-20-oxa-1-azabicyclo[20.4.0]hexacos-12-ene-3-carboxylate
• CAS: 133523-40-7
• 化学式: C₄₅H₇₃NO₁₃
• 分子量: 836.074
• InChiKey: VHFGORRTWQFADU-JNPBAIEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  59
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  199
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  甲醇 、 他克莫司 反应 3.0h， 以82%的产率得到methyl (4R,6S,7R,8S,10S,12E,14R,17S,18R,19S,22S)-3,7,17-trihydroxy-19-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-6,8-dimethoxy-4,10,12,18-tetramethyl-2,15,21-trioxo-14-prop-2-enyl-20-oxa-1-azabicyclo[20.4.0]hexacos-12-ene-3-carboxylate
  参考文献：
  名称：

  On the remarkable propensity for carbon-carbon bond cleavage reactions in the C(8)-C(10) region of FK-506

  摘要：

  It has been deduced from a series of transformations that formation of a tetrahedral intermediate at C-9 in FD-506 occasions fragmentation of the C-9-C-10 bond by a retro-Claisen-like pathway or the C-9-C-8 bond by a benzilic acid type rearrangement. Reduction of FK-506 with L-Selectride leads to the formation of a boronate ester 18 rather than to the corresponding diol 17, which had previously been formulated. Direct reduction of FK-506 with sodium triacetoxyborohydride (or hydrolysis of 18) does provide access to (22S)-dihydro FK-506 17. The former reduction also leads to some 22R epimer, which is an intermediate in the total synthesis of FK-506.

  DOI：

  10.1021/jo00008a055

文献信息

• Studies on the chemistry of rapamycin: Novel transformations under Lewis-acid catalysis
  作者：Juan I. Luengo、Arda L. Konialian、Dennis A. Holt

  DOI：10.1016/s0040-4039(00)77473-9

  日期：1993.2

  The reactivity of rapamycin under mild Lewis-acid catalysis has been investigated. The molecule has been found to be extremely sensitive to basic reagents due to carboxylate elimination beta to the C24 ketone. However, transformations normally effected under basic conditions, such as C-13-C-14 benzilic acid rearrangement Of C28-C30 retroaldol, can be achieved on rapamycin itself by catalysis with ZnCl2 in the appropriate solvent. These are novel transformations that circumvent the protection or masking of reactive functional groups and allow efficient degradation of the molecule for synthetic and biological studies.