H-MeLeu-Val-MeLeu-Ala-OBzl | 81135-28-6

• 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: H-MeLeu-Val-MeLeu-Ala-OBzl
• 英文别名: N-methylleucylvalyl-N-methylleucylalanine benzyl ester；Me-Leu-Val-(Me)Leu-Ala-OBzl；Me-Leu-Val-N(Me)Leu-Ala-OBn；benzyl (2S)-2-[[(2S)-4-methyl-2-[methyl-[(2S)-3-methyl-2-[[(2S)-4-methyl-2-(methylamino)pentanoyl]amino]butanoyl]amino]pentanoyl]amino]propanoate
• CAS: 81135-28-6
• 化学式: C₂₉H₄₈N₄O₅
• 分子量: 532.724
• InChiKey: XKEKABAMCPEUKA-LFBFJMOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  38
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  H-MeLeu-Val-MeLeu-Ala-OBzl 在 N-甲基吗啉 、 盐酸 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 31.0h， 生成 (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl-L-2-aminobutyrylsarcosyl-N-methylleucylvalyl-N-methylleucylalanine 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
• 作为产物：
  描述：

  Fmoc-N-甲基-L-亮氨酸 在 四(三苯基膦)钯 、 bis(2-oxo-3-oxazolidinyl)phosphoric acid chloride 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 5,5-二甲基-1,3-环己二酮 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 6.58h， 生成 H-MeLeu-Val-MeLeu-Ala-OBzl
  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。
• Modification of Cyclosporin A (CS): Generation of an enolate at the sarcosine residue and reactions with electrophiles
  作者：Dieter Seebach、Albert K. Beck、Hans G. Bossler、Christian Gerber、Soo Y Ko、C. William Murtiashaw、Reto Naef、Shin-Ichiro Shoda、Adrian Thaler、Manfred Krieger、Roland Wenger

  DOI：10.1002/hlca.19930760415

  日期：1993.6.30

  diisopropylamide (LDA) or BuLi) convert cyclosporin A (CS) to hexalithio derivative containing a Li alkoxide, four Li azaenolate, and one Li enolate units. The Li6 compound is solubilized in tetrahydrofuran (THF) by addition of excess LDA or LiCl. Reactions with electrophiles (alkyl halides, aldehydes, ClCO2R, CO2, (RS)2, D2O) at low temperatures give products containing new side chains in amino-acid residue

  强碱（二异丙基氨基化锂（LDA）或BuLi）可将环孢菌素A（CS）转化为含有Li醇盐，四个Li azaenolate和一个Li enolate单​​元的六硫代衍生物。通过添加过量的LDA或LiCl将Li 6化合物溶解在四氢呋喃（THF）中。与亲电反应（烷基卤化物，醛，ClCO 2 R，CO 2，（RS）2，d 2 O）在低温下得到含有在循环十一肽的氨基酸残基3个新的侧链产物（参见1 - 13，方案1和2，以及图1和2）在较高产率，并且与再-或硅-selectivities，取决于向上的锂化至7中的条件：1，纯CS衍生物（方案2，表1中。EXPER部分）可通过柱色谱法来分离。Ñ -Alkylations或通过羰基加入肽骨架的裂解仅在较高的温度和/或与延长的反应时间（见发生14和15在方案4）。在所采用的条件下，很少或没有立体异构中心的差向异构化发生。讨论了CS进行这些令人惊讶的转换的可行性的
• 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：——
• 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
  作者：Peng Li、Jie Cheng Xu

  DOI：10.1021/jo991687c

  日期：2000.5.1

  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.
• 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