methyl (4aR,7S,7aS)-7-formyl-6-[(4-methoxyphenyl)methyl]-2,2,7a-trimethyl-5-oxo-4,4a-dihydro-3H-oxasilino[5,6-c]pyrrole-7-carboxylate | 704910-38-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (4aR,7S,7aS)-7-formyl-6-[(4-methoxyphenyl)methyl]-2,2,7a-trimethyl-5-oxo-4,4a-dihydro-3H-oxasilino[5,6-c]pyrrole-7-carboxylate
• CAS: 704910-38-3
• 化学式: C₂₀H₂₇NO₆Si
• 分子量: 405.523
• InChiKey: AAAUXQFIJPFZHK-VDGAXYAQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.15
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(3R,3aS,7aR)-3-Hydroxymethyl-2-(4-methoxy-benzyl)-3a,5,5-trimethyl-1-oxo-octahydro-4-oxa-2-aza-5-sila-indene-3-carboxylic acid methyl ester	704910-44-1	C20H29NO6Si	407.539
  ——	(3R,3aS,7aR)-3-Benzyloxymethyl-2-(4-methoxy-benzyl)-3a,5,5-trimethyl-1-oxo-octahydro-4-oxa-2-aza-5-sila-indene-3-carboxylic acid methyl ester	704910-37-2	C27H35NO6Si	497.663
  ——	methyl (2R,3S)-1-(4-methoxybenzyl)-2-((benzyloxy)methyl)-3-hydroxy-3-methyl-4-methylene-5-oxopyrrolidine-2-carboxaldehyde	704910-34-9	C24H27NO6	425.481
  ——	methyl (R)-2-(N-(4-methoxybenzyl)acrylamido)-2-((benzyloxy)methyl)-3-oxybutanoate	704910-33-8	C24H27NO6	425.481

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(3R,3aS,7aR)-3-((S)-1-Hydroxy-2-methyl-propyl)-2-(4-methoxy-benzyl)-3a,5,5-trimethyl-1-oxo-octahydro-4-oxa-2-aza-5-sila-indene-3-carboxylic acid methyl ester	857681-75-5	C23H35NO6Si	449.62
  ——	(3R,3aS,7aR)-3-[(S)-1-(Isopropyl-dimethyl-silanyloxy)-2-methyl-propyl]-2-(4-methoxy-benzyl)-3a,5,5-trimethyl-1-oxo-octahydro-4-oxa-2-aza-5-sila-indene-3-carboxylic acid methyl ester	857681-81-3	C28H47NO6Si2	549.855
  ——	methyl (4aR,7R,7aS)-7-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-6-[(4-methoxyphenyl)methyl]-2,2,7a-trimethyl-5-oxo-4,4a-dihydro-3H-oxasilino[5,6-c]pyrrole-7-carboxylate	704910-39-4	C26H37NO6Si	487.668
  ——	(2R,3S,4R)-3-Hydroxy-4-(2-hydroxy-ethyl)-2-[(S)-1-(isopropyl-dimethyl-silanyloxy)-2-methyl-propyl]-1-(4-methoxy-benzyl)-3-methyl-5-oxo-pyrrolidine-2-carboxylic acid methyl ester	857681-76-6	C26H43NO7Si	509.715
  ——	(2R,3S,4R)-2-[(S)-{(S)-cyclohex-2-enyl}hydroxymethyl]-3-hydroxy-4-(2-hydroxyethyl)-1-(4-methoxybenzyl)-3-methyl-5-oxopyrrolidine-2-carboxylic acid methyl ester	704910-41-8	C24H33NO7	447.529
  ——	(2R,3S,4R)-3-Hydroxy-4-(2-hydroxy-ethyl)-2-[(S)-1-(isopropyl-dimethyl-silanyloxy)-2-methyl-propyl]-3-methyl-5-oxo-pyrrolidine-2-carboxylic acid methyl ester	857681-77-7	C18H35NO6Si	389.565
  ——	(1R,4R,5S)-4-(2-Chloro-ethyl)-1-[(S)-1-(isopropyl-dimethyl-silanyloxy)-2-methyl-propyl]-5-methyl-6-oxa-2-aza-bicyclo[3.2.0]heptane-3,7-dione	857681-82-4	C17H30ClNO4Si	375.968
  ——	(2R,3S,4R)-3-Hydroxy-4-(2-hydroxy-ethyl)-2-[(S)-1-(isopropyl-dimethyl-silanyloxy)-2-methyl-propyl]-3-methyl-5-oxo-pyrrolidine-2-carboxylic acid	861927-69-7	C17H33NO6Si	375.538
  ——	(1R,4R,5S)-4-(2-chloroethyl)-1-((R)-2,2-difluoro-1-hydroxybut-3-en-1-yl)-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione	1367878-64-5	C12H14ClF2NO4	309.697
  马里佐米	salinosporamide A	437742-34-2	C15H20ClNO4	313.781

反应信息

• 作为反应物：
  描述：

  methyl (4aR,7S,7aS)-7-formyl-6-[(4-methoxyphenyl)methyl]-2,2,7a-trimethyl-5-oxo-4,4a-dihydro-3H-oxasilino[5,6-c]pyrrole-7-carboxylate 在 potassium fluoride 、 lithium hydroxide 、 ammonium cerium(IV) nitrate 、 双氧水 、 potassium hydrogencarbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 120.0h， 生成 (2R,3S,4R)-2-((S)-((S)-cyclohex-2-en-1-yl)(hydroxy)methyl)-3-hydroxy-4-(2-hydroxyethyl)-3-methyl-5-oxopyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  salinosporamide A的简单立体控制合成。

  摘要：

  已经开发了简单有效的立体合成唾液孢酰胺A的合成方法。该方法是唾液孢酰胺A的首次合成，能够提供大量化合物用于进一步的生物学研究。Salinosporamide A作为合成靶标特别受关注，因为它对许多肿瘤细胞系具有强大的体外细胞毒活性（IC（50）值为10 nM或更小）。

  DOI：

  10.1021/ja048613p
• 作为产物：
  描述：

  (3R,3aS,7aR)-3-Benzyloxymethyl-2-(4-methoxy-benzyl)-3a,5,5-trimethyl-1-oxo-octahydro-4-oxa-2-aza-5-sila-indene-3-carboxylic acid methyl ester 在 palladium on activated charcoal 氢气 、 戴斯-马丁氧化剂 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 23.0 ℃ 、101.33 kPa 条件下， 反应 13.0h， 生成 methyl (4aR,7S,7aS)-7-formyl-6-[(4-methoxyphenyl)methyl]-2,2,7a-trimethyl-5-oxo-4,4a-dihydro-3H-oxasilino[5,6-c]pyrrole-7-carboxylate
  参考文献：
  名称：

  salinosporamide A的简单立体控制合成。

  摘要：

  已经开发了简单有效的立体合成唾液孢酰胺A的合成方法。该方法是唾液孢酰胺A的首次合成，能够提供大量化合物用于进一步的生物学研究。Salinosporamide A作为合成靶标特别受关注，因为它对许多肿瘤细胞系具有强大的体外细胞毒活性（IC（50）值为10 nM或更小）。

  DOI：

  10.1021/ja048613p

文献信息

• Simple stereocontrolled synthesis of salinosporamide A
  申请人：Corey J. Elias

  公开号：US20050228186A1

  公开（公告）日：2005-10-13

  A simple and effective stereocontrolled synthesis of salinosporamide A (1) has been developed which follows the pathway outlined in the Figure. The process, the first total synthesis of salinosporamide A, is capable of providing the compound in substantial quantities for further biological studies. In addition to the method of Scheme I, the present invention also includes several novel synthetic intermediate compounds, several intermediate steps of the preferred synthetic process; and the uses of these compounds in the preparation of synthetic derivatives of the compound Salinosporamide A. Salinosporamide A is of special interest as a synthetic target because of its protein in vitro cytotoxic activity against many tumor cell lines (IC 50 values of 10 nM or less).

  已经开发出一种简单而有效的立体控制合成方法，用于制备Salinosporamide A (1)，该方法遵循图中概述的途径。这个过程是对Salinosporamide A的首次全合成，能够提供大量的化合物用于进一步的生物研究。除了方案I的方法之外，本发明还包括几种新颖的合成中间体化合物，首选合成过程的几个中间步骤；以及这些化合物在制备Salinosporamide A的合成衍生物中的用途。Salinosporamide A作为合成目标具有特殊的意义，因为它在体外对许多肿瘤细胞系的蛋白细胞毒活性(IC50值为10 nM或更低)。
• [EN] ANALOGS OF SALINOSPORAMIDE A<br/>[FR] ANALOGUES DE SALINOSPORAMIDE A
  申请人：HARVARD COLLEGE

  公开号：WO2005099687A3

  公开（公告）日：2005-12-29
• Coupling of sterically hindered aldehyde with fluorinated synthons: Stereoselective synthesis of fluorinated analogues of salinosporamide A
  作者：Zeng-Hao Chen、Bing-Lin Wang、Andrew J. Kale、Bradley S. Moore、Ruo-Wen Wang、Feng-Ling Qing

  DOI：10.1016/j.jfluchem.2012.01.003

  日期：2012.4

  Salinosporamide A is an irreversible inhibitor of the beta-subunits of the 20S proteasome. Its C-5 cyclohexenyl moiety is the key to its affinity and potency as an anticancer agent. Here we describe the synthesis of C-5 difluoromethylated and trifluoromethylated analogues of salinosporamide A and their biological evaluation as proteasome inhibitors against purified yeast 20S proteasome. The synthetic strategy featured the stereoselective coupling reaction of sterically hindered aldehyde 3 with fluorinated organolithium reagents. (C) 2012 Elsevier B.V. All rights reserved.
• A Simple Stereocontrolled Synthesis of Salinosporamide A
  作者：Leleti Rajender Reddy、P. Saravanan、E. J. Corey

  DOI：10.1021/ja048613p

  日期：2004.5.1

  A simple and effective stereocontrolled synthesis of salinosporamide A has been developed. This process, the first synthesis of salinosporamide A, is capable of providing the compound in substantial quantities for further biological studies. Salinosporamide A was of special interest as a synthetic target because of its potent in vitro cytotoxic activity against many tumor cell lines (IC(50) values

  已经开发了简单有效的立体合成唾液孢酰胺A的合成方法。该方法是唾液孢酰胺A的首次合成，能够提供大量化合物用于进一步的生物学研究。Salinosporamide A作为合成靶标特别受关注，因为它对许多肿瘤细胞系具有强大的体外细胞毒活性（IC（50）值为10 nM或更小）。
• New Synthetic Route for the Enantioselective Total Synthesis of Salinosporamide A and Biologically Active Analogues
  作者：Leleti Rajender Reddy、Jean-François Fournier、B. V. Subba Reddy、E. J. Corey

  DOI：10.1021/ol0508734

  日期：2005.6.1

  [reaction: see text] A total synthesis of the salinosporamide analogue 3 is described that starts with the novel cyclization 4 --> 5.

  [反应：见正文]描述了从新的环化反应4-> 5开始的盐孢酰胺类似物3的总合成。