(2R,3S)-3-((S)-1-(叔丁氧基羰基)吡咯烷-2-基)-3-甲氧基-2-甲基丙酸 | 157967-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: (2R,3S)-3-((S)-1-(叔丁氧基羰基)吡咯烷-2-基)-3-甲氧基-2-甲基丙酸
• 英文名称: N-(tert-Butoxycarbonyl)-(2R,3S,2'S)-dolaproine
• 英文别名: <2S-<2R*,α(S*),β(R*)>>-1-<(1,1-Dimethylethoxy)carbonyl>-β-methoxy-α-methyl-2-pyrrolidinepropanoic acid；(2R,3S,4S)-3-(N-tert-butoxycarbonyl-2'-pyrrolidinyl)-3-methoxy-2-methylpropanoic acid；(2R,3S)-3-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoic acid；(2R,3S)-3-methoxy-2-methyl-3-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]propanoic acid
• CAS: 157967-06-1
• 化学式: C₁₄H₂₅NO₅
• 分子量: 287.356
• InChiKey: LNEHHTWYEBGHBY-VWYCJHECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3S)-3-((S)-1-(叔丁氧基羰基)吡咯烷-2-基)-3-甲氧基-2-甲基丙酸 、 (1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethan-1-amine trifluoroacetic acid salt 在 氰基磷酸二乙酯 、 三乙胺 作用下， 以 乙二醇二甲醚 为溶剂， 以55%的产率得到N-(tert-Butoxycarbonyl)-(9R,10S,11S)-iso-dolaproinyl-dolaphenine
  参考文献：
  名称：

  The Dolastatins. 22. Synthesis Of Boc-Dolaproinyl Dolaphenine and Four Related Chiral Isomers

  摘要：

  Synthesis of the dolastatin 10 (1) dipeptide segment N-(tert-butoxycarbonyl)-dolaproinyl-dolaphenine (2, Boc-Dap-Doe) and four chiral isomers (3-5, 13) has been summarized. Formation of the amide bond was readily accomplished employing diethyl cyanophosphonate. The stereochemical assignments for Boc-Dap-Doe (2) and Boc-Dap-(6R)-Doe (3) were confirmed by X-ray crystal structure analyses.

  DOI：

  10.1021/jo00090a009
• 作为产物：
  描述：

  (S)-N-Boc-吡咯烷-2-甲醛 N-(叔丁氧羰基)-L-脯氨醛 在 palladium on activated charcoal 正丁基锂 、 Proton Sponge 、 氢气 、 二异丙胺 、 magnesium bromide 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 65.5h， 生成 (2R,3S)-3-((S)-1-(叔丁氧基羰基)吡咯烷-2-基)-3-甲氧基-2-甲基丙酸
  参考文献：
  名称：

  The Dolastatins. 17. Synthesis of Dolaproine and Related Diastereoisomers

  摘要：

  A special challenge in accomplishing the total synthesis of dolastatin 10(1) entailed deducing the absolute configuration of the new beta-methoxy-gamma-amino acid component dolaproine (2) as 2S,2'R,3'R and devising a stereoselective synthesis. Synthesis of this unusual (S)-proline-derived unit as its N-tert-butoxycarbonyl derivative (9b) and three stereoisomers (9a, 9c, 9d) has been summarized. The diastereoisomers were assembled by an aldol condensation between aldehyde 5, derived from (S)-proline, with chiral propionate 6, followed by methylation and cleavage of the chiral directing ester group by hydrogenolysis to afford methyl ethers 9a-d. The absolute stereochemistry of the diastereoisomers was determined by a combination of X-ray crystallographic analyses (of 9a and lactam 11b formed from isomer 7a) and high-field (400 MHz) NMR studies. By using each of these isomers in a series of dolastatin 10 syntheses the stereochemistry of the dolaproine (2) unit of natural (-)-dolastatin 10 (1) was shown to be 2S,2'R,3'R.

  DOI：

  10.1021/jo00100a034

文献信息

• Synthesis of both syn and anti diastereoisomers of Boc-dolaproine from (S)-proline through DKR using ruthenium-catalyzed hydrogenation: a dramatic role of N-protecting groups
  作者：Céline Mordant、Sébastien Reymond、Virginie Ratovelomanana-Vidal、Jean-Pierre Genêt

  DOI：10.1016/j.tet.2004.07.043

  日期：2004.10

  The natural (2R,3R)-Boc-dolaproine and its unnatural (2S,3S) diastereoisomer were synthesized involving as key transformation the Ru(II)-promoted hydrogenation of the beta-keto-alpha-methyl ester derived from (S)-N-Boc-proline. Interestingly, the asymmetric hydrogenation of this beta-keto ester N-protected as an amine hydrochloride salt, provided the corresponding anti (2S,3R)- and (2R,3S)-beta-hydroxy-alpha-methyl esters with significant level of selectivities through dynamic kinetic resolution. (C) 2004 Elsevier Ltd. All rights reserved.
• The Dolastatins. 17. Synthesis of Dolaproine and Related Diastereoisomers
  作者：George R. Pettit、Sheo Bux Singh、Delbert L. Herald、Paul Lloyd-Williams、Darko Kantoci、Douglas D. Burkett、Jozsef Barkoczy、Fiona Hogan、Terah R. Wardlaw

  DOI：10.1021/jo00100a034

  日期：1994.10

  A special challenge in accomplishing the total synthesis of dolastatin 10(1) entailed deducing the absolute configuration of the new beta-methoxy-gamma-amino acid component dolaproine (2) as 2S,2'R,3'R and devising a stereoselective synthesis. Synthesis of this unusual (S)-proline-derived unit as its N-tert-butoxycarbonyl derivative (9b) and three stereoisomers (9a, 9c, 9d) has been summarized. The diastereoisomers were assembled by an aldol condensation between aldehyde 5, derived from (S)-proline, with chiral propionate 6, followed by methylation and cleavage of the chiral directing ester group by hydrogenolysis to afford methyl ethers 9a-d. The absolute stereochemistry of the diastereoisomers was determined by a combination of X-ray crystallographic analyses (of 9a and lactam 11b formed from isomer 7a) and high-field (400 MHz) NMR studies. By using each of these isomers in a series of dolastatin 10 syntheses the stereochemistry of the dolaproine (2) unit of natural (-)-dolastatin 10 (1) was shown to be 2S,2'R,3'R.
• The Dolastatins. 22. Synthesis Of Boc-Dolaproinyl Dolaphenine and Four Related Chiral Isomers
  作者：George R. Pettit、Jozsef Barkoczy、Jayaram K. Srirangam、Sheo Bux Singh、Delbert L. Herald、Michael D. Williams、Darko Kantoci、Fiona Hogan、Thomas L. Groy

  DOI：10.1021/jo00090a009

  日期：1994.6

  Synthesis of the dolastatin 10 (1) dipeptide segment N-(tert-butoxycarbonyl)-dolaproinyl-dolaphenine (2, Boc-Dap-Doe) and four chiral isomers (3-5, 13) has been summarized. Formation of the amide bond was readily accomplished employing diethyl cyanophosphonate. The stereochemical assignments for Boc-Dap-Doe (2) and Boc-Dap-(6R)-Doe (3) were confirmed by X-ray crystal structure analyses.