Dimethyl 2-(phenylseleno)-8-(phenylsulfonyl)-1,2(R),3,3a(R),8,8a(S)-hexahydropyrrolo<2,3-b>indole-1,2-dicarboxylate | 145642-79-1

• 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: Dimethyl 2-(phenylseleno)-8-(phenylsulfonyl)-1,2(R),3,3a(R),8,8a(S)-hexahydropyrrolo<2,3-b>indole-1,2-dicarboxylate
• CAS: 145642-79-1
• 化学式: C₂₆H₂₄N₂O₆SSe
• 分子量: 571.512
• InChiKey: YZLZZFQZUNGNGG-VIICAESSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  36.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  93.22
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  Dimethyl 2-(phenylseleno)-8-(phenylsulfonyl)-1,2(R),3,3a(R),8,8a(S)-hexahydropyrrolo<2,3-b>indole-1,2-dicarboxylate 在 sodium hydride 、 二甲基亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 10.5h， 生成 Dimethyl 2,3-methano-8-(phenylsulfonyl)-1,2(S),3(S),3a(R),8,8a(S)-hexahydropyrrolo<2,3-b>indole-1,2-dicarboxylate
  参考文献：
  名称：

  Cyclic Tautomers of Tryptophan: Enantio- and Diastereoselective Synthesis of .beta.-Substituted and .alpha.,.beta.-Disubstituted Derivatives of Tryptophan

  摘要：

  A method is presented for the synthesis of enantiomerically pure erythro-beta-alkylated derivatives of L-tryptophan from L-tryptophan itself via the intermediacy of cyclic tryptophan tautomers. Dehydrogenation of the cyclic tryptophan tautomer 2 to 3 is achieved via either the 2-phenylseleno derivative 6 or its 8-phenylthio counterpart 7 by oxidation to the corresponding selenoxide or sulfoxide and formal syn-elimination. Evidence is provided that this elimination proceeds, at least in part, by a stepwise rather than a concerted pericyclic mechanism. Soft nucleophiles, including thiolates, amines, and higher order cuprates, add to 3 in conjugate fashion in high yield and with excellent diastereoselectivity from the exe-face of the bicyclic system. The enolate anion resulting from conjugate addition is likewise quenched with high selectivity from the exo face either by simple protonation or by alkylation with methyl iodide. The tetrahydropyrroloindole 3 also reacts with cyclopentadiene in a Diels-Alder reaction with excellent selectivity to give 29. Sulfur ylide chemistry enables the formation of the cyclopropane adduct 27. After conjugate addition, cycloreversion to the tryptophan skeleton is achieved by dissolution in trifluoroacetic acid. The rate of ring opening is strongly dependant on the steric bulk and orientation of the substituent at C-3, with large exo-substituents strongly retarding ring opening and endo-substituents favoring ring opening. Desulfonylation is achieved by photolysis with ascorbic acid and anisole and final deprotection by heating to reflux with 6 M hydrochloric acid. Desulfonylation of the 2,3-methano derivative 37 resulted in degradation of the cyclopropane ring. Use of a (4-methoxyphenyl)sulfonyl group in place of the phenylsulfonyl group, as in 11 and 22, enables one-step desulfonylation and ring opening by treatment with methanesulfonic acid.

  DOI：

  10.1021/jo00094a041
• 作为产物：
  描述：

  苯基氯化硒 、 α-甲基色氨酸前体 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 以70%的产率得到Dimethyl 2-(phenylseleno)-8-(phenylsulfonyl)-1,2(R),3,3a(R),8,8a(S)-hexahydropyrrolo<2,3-b>indole-1,2-dicarboxylate
  参考文献：
  名称：

  Cyclic Tautomers of Tryptophan: Enantio- and Diastereoselective Synthesis of .beta.-Substituted and .alpha.,.beta.-Disubstituted Derivatives of Tryptophan

  摘要：

  A method is presented for the synthesis of enantiomerically pure erythro-beta-alkylated derivatives of L-tryptophan from L-tryptophan itself via the intermediacy of cyclic tryptophan tautomers. Dehydrogenation of the cyclic tryptophan tautomer 2 to 3 is achieved via either the 2-phenylseleno derivative 6 or its 8-phenylthio counterpart 7 by oxidation to the corresponding selenoxide or sulfoxide and formal syn-elimination. Evidence is provided that this elimination proceeds, at least in part, by a stepwise rather than a concerted pericyclic mechanism. Soft nucleophiles, including thiolates, amines, and higher order cuprates, add to 3 in conjugate fashion in high yield and with excellent diastereoselectivity from the exe-face of the bicyclic system. The enolate anion resulting from conjugate addition is likewise quenched with high selectivity from the exo face either by simple protonation or by alkylation with methyl iodide. The tetrahydropyrroloindole 3 also reacts with cyclopentadiene in a Diels-Alder reaction with excellent selectivity to give 29. Sulfur ylide chemistry enables the formation of the cyclopropane adduct 27. After conjugate addition, cycloreversion to the tryptophan skeleton is achieved by dissolution in trifluoroacetic acid. The rate of ring opening is strongly dependant on the steric bulk and orientation of the substituent at C-3, with large exo-substituents strongly retarding ring opening and endo-substituents favoring ring opening. Desulfonylation is achieved by photolysis with ascorbic acid and anisole and final deprotection by heating to reflux with 6 M hydrochloric acid. Desulfonylation of the 2,3-methano derivative 37 resulted in degradation of the cyclopropane ring. Use of a (4-methoxyphenyl)sulfonyl group in place of the phenylsulfonyl group, as in 11 and 22, enables one-step desulfonylation and ring opening by treatment with methanesulfonic acid.

  DOI：

  10.1021/jo00094a041

文献信息

• Conformationally restricted amino acids: Diastereoselective substitution at the β-position of L-tryptophan
  作者：Milan Bruncko、David Crich

  DOI：10.1016/s0040-4039(00)60945-0

  日期：1992.10

  Higher order cuprates add with extreme exo-facial selectivity to the chiral tetrahydropyrroloindole 3, itself prepared in enantiomerically pure form from L-tryptophan: treatment of the adducts with trifluoroacetic acid provides diastereo- and enantiomerically pure beta-substituted tryptophan derivatives.