(2S,3S)-3-((S)-1-(叔丁氧基羰基)吡咯烷-2-基)-3-甲氧基-2-甲基丙酸 | 157967-07-2

• 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: (2S,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: (2S,3S,4S)-3-(N-tert-butoxycarbonyl-2'-pyrrolidinyl)-3-methoxy-2-methylpropanoic acid
• 英文别名: (2S,3S)-3-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoic acid；(2S,3S)-3-methoxy-2-methyl-3-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]propanoic acid
• CAS: 157967-07-2
• 化学式: C₁₄H₂₅NO₅
• 分子量: 287.356
• InChiKey: LNEHHTWYEBGHBY-DCAQKATOSA-N

物化性质

• 沸点：
  397.8±17.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)

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：

  (2S,3S)-3-((S)-1-(叔丁氧基羰基)吡咯烷-2-基)-3-甲氧基-2-甲基丙酸 在 三氟乙酸 作用下， 以 乙醚 为溶剂， 反应 0.25h， 生成 (2S,3S)-3-Methoxy-2-methyl-3-(S)-pyrrolidin-2-yl-propionic acid methyl ester
  参考文献：
  名称：

  Synthése de la dolastatine 10 et de la [R-doe]-dolastatine 10

  摘要：

  A stepwise synthesis of dolastatin 10 starting from the dolaphenine residue is described. The chiral dola isoleuine and dolaproine residues were obtained by 5-step procedures from the corresponding N-Boc amino acid. The key steps are respectively the NaBH4 reduction of an allylic ketone and the addition of an achiral Z-crotylboronate on the N-Boc-L-prolinal. Peptidic couplings were efficiently realised with reagents developed in the laboratory.

  DOI：

  10.1016/s0040-4020(01)80692-x
• 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 89.5h， 生成 (2S,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 and antiproliferative activity of a cyclic analog of dolastatin 10
  作者：Joël Poncet、Laurent Hortala、Magali Busquet、Françoise Guéritte-Voegelein、Sylvie Thoret、Alain Pierré、Ghanem Atassi、Patrick Jouin

  DOI：10.1016/s0960-894x(98)00511-3

  日期：1998.10

  A cyclic analog of the natural antiproliferative compound dolastatin 10 was synthesized by introducing an ester link between the N- and C-terminal residues which were modified accordingly. The final macrolactonization was performed by using isopropenyl chloroformate and DMAP as reagents. This analog exhibits submicromolar antiproliferative activity against the L1210 and HT29 cell lines and inhibits in vitro tubulin polymerization (IC50, 39 mu M). (C) 1998 Elsevier Science Ltd. All lights reserved.
• 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.
• 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.
• Synthése de la dolastatine 10 et de la [R-doe]-dolastatine 10
  作者：Florence Roux、Isabelle Maugras、Joël Poncet、Gilles Niel、Patrick Jouin

  DOI：10.1016/s0040-4020(01)80692-x

  日期：1994.5

  A stepwise synthesis of dolastatin 10 starting from the dolaphenine residue is described. The chiral dola isoleuine and dolaproine residues were obtained by 5-step procedures from the corresponding N-Boc amino acid. The key steps are respectively the NaBH4 reduction of an allylic ketone and the addition of an achiral Z-crotylboronate on the N-Boc-L-prolinal. Peptidic couplings were efficiently realised with reagents developed in the laboratory.