N-methyl-L-leucyl-L-alanine benzyl ester | 81135-25-3

• 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: N-methyl-L-leucyl-L-alanine benzyl ester
• 英文别名: N-methylleucylalanine benzyl ester；Me-Leu-Ala-OBzl；benzyl (2S)-2-[[(2S)-4-methyl-2-(methylamino)pentanoyl]amino]propanoate
• CAS: 81135-25-3
• 化学式: C₁₇H₂₆N₂O₃
• 分子量: 306.405
• InChiKey: ZFMQZPJLAWVIIN-ZFWWWQNUSA-N

物化性质

• 沸点：
  443.8±30.0 °C(Predicted)
• 密度：
  1.055±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-methyl-L-leucyl-L-alanine benzyl ester 在 2-bromo-1-ethylpyridin-1-ium tetrafluoroborate 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.67h， 生成 L-valyl-N-methyl-L-leucyl-L-alanine benzyl ester
  参考文献：
  名称：

  Total Synthesis of Cyclosporin O Both in Solution and in the Solid Phase Using Novel Thiazolium-, Immonium-, and Pyridinium-Type Coupling Reagents:  BEMT, BDMP, and BEP¹

  摘要：

  Cyclosporin O (1), an extensively N-methylated immunosuppressive cyclic undecapeptide isolated from Tolypocladium inflatum Gams, was synthesized in 20-23% overall yield via 4 + 7 segment condensation and cyclization by the combined utilization of novel thiazolium- and immonium-type peptide coupling reagents 2-bromo-3-ethyl-4-methyl thiazolium tetrafluoroborate (BEMT) and 5-(1H-benzotriazol-1-yloxy)-3,4-dihydro-1-methyl 2H-pyrrolium hexachloroantimonate (BDMP) as well as compound 2-bromo-1-ethyl pyridinium tetrafluoroborate (BEP). BEMT and BEP, which have been proven to be very efficient for the coupling of peptide segments containing N-alkylated amino acid residues with respect to the fast reaction speed, low racemization, and high yields, were used to construct hindered amide bonds in CsO with the addition of HOAt, whereas the most efficient HOBt-derived immonium type reagent, BDMP, was used to perform the coupling of coded amino acids in CsO. Thus, the highly hindered protected 8-11 tetrapeptide 25 was successfully synthesized using BEMT in 65% yield, and the 1-7 heptapeptide 21 was obtained in 52-55% yield by the rationally combined utilization of BDMP, BEMT, and BEP. The synthesis of the linear undecapeptide 27 of CsO in the solid phase using BEMT and BEP was accomplished for the further evaluation of the effectiveness of these reagents.

  DOI：

  10.1021/jo991687c
• 作为产物：
  描述：

  Fmoc-N-甲基-L-亮氨酸 在 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.5h， 生成 N-methyl-L-leucyl-L-alanine benzyl ester
  参考文献：
  名称：

  Synthesis of D-lysine8-cyclosporine A. Further characterization of BOP-Cl in the 2-7 hexapeptide fragment synthesis

  摘要：

  DOI：

  10.1021/jo00296a061

文献信息

• Total Synthesis of Cyclosporin O by Convergent Approach Employing Fmoc-Amino Acid Chlorides Mediated by Zinc Dust
  作者：Subramanyam J Tantry、Rao Venkataramanarao、Gundala Chennakrishnareddy、Vommina Venkata Sureshbabu

  DOI：10.1021/jo701329w

  日期：2007.11.1

  An epimerization free and efficient total synthesis of immunosuppressant cyclosporin O (CsO) by step-by-step assembly of amino acids in solution phase is reported. The couplings were performed by employing Fmoc-amino acid chlorides and were mediated by zinc dust under neutral conditions. The yield and purity of the coupling of sterically hindered N-methylamino acids to N-methylamino acids at positions

  据报道，通过在溶液相中逐步组装氨基酸，可实现无差向异构和高效的免疫抑制剂环孢菌素O（CsO）的全合成。通过使用Fmoc-氨基酸氯化物进行偶联，并在中性条件下由锌粉介导。的空间耦合的产率和纯度受阻Ñ甲基氨基酸以Ñ甲基氨基酸在位置8，9，10，和11通过在这些特定接合点重复三次耦合增强。分离出与CsO和最终CsO有关的所有10种中间肽，并通过IR，1 H NMR，质谱和HPLC技术对其进行了完全表征。
• Synthesis of cyclosporine. Total syntheses of ?cyclosporin A? and ?cyclosporin H?, two fungal metabolites isolated from the speciesTolypocladium inflatum GAMS
  作者：Roland M. Wenger

  DOI：10.1002/hlca.19840670220

  日期：1984.3.14

  al-MeLeu-Ala-OBzl (20) was synthesized for coupling with the previously described cyclosporine tetrapeptide sequence Boc-D-Ala-MeLeu-MeVal-OH (21). The product of the coupling, the undecapeptide Boc-D-Ala-MeLeu-MeLeu-MeVal-MeBmt-abu-Sar-MeLeu-Val-MeLeu-Ala-OBzl (22), was then deprotected and cyclized to cyclosporine (1).

  合成七肽H-MeBmt-Abu-Sar-MeLeu-Val-MeLeu-Ala-OBzl（20）以与先前描述的环孢素四肽序列Boc-D-Ala-MeLeu-MeVal-OH（21）偶联。然后将偶联的产物十一肽Boc-D-Ala-MeLeu-MeLeu-MeVal-MeBmt-abu-Sar-MeLeu-Val-MeLeu-Ala-OBzl（22）脱保护并环化为环孢霉素（1）。
• Stereoselective Synthesis of [5-[4,4,4,4′,4′,4′-Hexafluoro-N-(2-hydroxyethoxy)-D-valine]]- and [5-[4,4,4,4′,4′,4′-Hexafluoro-N-(2-hydroxyethoxy)-L-valine]cyclosporin A
  作者：Marcel K. Eberle、Reinhart Keese

  DOI：10.1002/hlca.201000175

  日期：——

  AbstractAddition of various amines to the 3,3‐bis(trifluoromethyl)acrylamides 10a and 10b gave the tripeptides 11a–11f, mostly as mixtures of epimers (Scheme 3). The crystalline tripeptide 11f2 was found to be the N‐terminal (2‐hydroxyethoxy)‐substituted (R,S,S)‐ester HOCH2CH2O‐D‐Val(F6)‐MeLeu‐Ala‐OtBu by X‐ray crystallography. The C‐terminal‐protected tripeptide 11f2 was condensed with the N‐terminus octapeptide 2b to the depsipeptide 12a which was thermally rearranged to the undecapeptide 13a (Scheme 4). The condensation of the epimeric tripeptide 11f1 with the octapeptide 2b gave the undecapeptide 13b directly. The undecapeptides 13a and 13b were fully deprotected and cyclized to the [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐D‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐L‐valine]]cyclosporins 14a and 14b, respectively (Scheme 5). Rate differences observed for the thermal rearrangements of 12a to 13a and of 12b to 13b are discussed.
• Synthesis of D-lysine8-cyclosporine A. Further characterization of BOP-Cl in the 2-7 hexapeptide fragment synthesis
  作者：William J. Colucci、Roger D. Tung、John A. Petri、Daniel H. Rich

  DOI：10.1021/jo00296a061

  日期：1990.4
• COLUCCI, WILLIAM J.;TUNG, ROGER D.;PETRI, JOHN A.;RICH, DANIEL H., J. ORG. CHEM., 55,(1990) N, C. 2895-2903
  作者：COLUCCI, WILLIAM J.、TUNG, ROGER D.、PETRI, JOHN A.、RICH, DANIEL H.

  DOI：——

  日期：——