N-叔丁氧羰基-N(咪唑)-(4-甲基苯磺酰基)-L-组氨酸 | 35899-43-5

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 组氨酸类衍生物
• 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
• 中文名称: N-叔丁氧羰基-N(咪唑)-(4-甲基苯磺酰基)-L-组氨酸
• 中文别名: Nα-Boc-τ-甲苯磺酰基-L-组氨酸；BOC-L-组氨酸(对甲苯磺酰)；Nα-Boc-N(im)-甲苯磺酰基-L-组氨酸；NΑ-BOC-N(IM)-甲苯磺酰基-L-组胺酸；Nα-(叔丁氧羰基)-τ-(对甲苯磺酰基)-L-组氨酸；NAlpha-(叔丁氧羰基)-τ-(对甲苯磺酰基)-L-组氨酸；NΑ-(叔丁氧羰基)-Τ-对甲苯磺酰基-L-组氨酸
• 英文名称: Boc-His(Tos)-OH
• 英文别名: Boc-NH-L-His(Tos)-OH；(2S)-3-[1-(4-methylphenyl)sulfonylimidazol-4-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 35899-43-5
• 化学式: C₁₈H₂₃N₃O₆S
• mdl: MFCD00065967
• 分子量: 409.463
• InChiKey: DCLJSEPKYJSEHW-HNNXBMFYSA-N

物化性质

• 熔点：
  ~125 °C (dec.)
• 密度：
  1.19
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.388
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  2933290090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-叔丁氧羰基-N(咪唑)-(4-甲基苯磺酰基)-L-组氨酸 在 diethylphosphoryl cyanide 、 氰基磷酸二乙酯 、 sodium hydride 、 1-羟基苯并三唑 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 地替吉仑
  参考文献：
  名称：

  设计和合成具有延长的体内作用时间的有效的特异性肾素抑制剂。

  摘要：

  对含有主链Cα-甲基和Nα-甲基修饰的肽进行结构活性分析导致发现了具有高代谢稳定性的有效肾素抑制剂。在体外，Boc-Pro-Phe-Nα-MeHis-Leupsi- [CHOHCH2] Val-Ile-Amp（XII）是人血浆肾素的有效抑制剂，IC50为0.26 nM。它是其他天冬氨酸蛋白酶（如猪胃蛋白酶或牛组织蛋白酶D）的弱得多的抑制剂（IC50 = 6 microM）。已表明它不会被大鼠肝匀浆制剂降解。在体内，它抑制了血浆血浆肾素的活性并降低了呋塞米治疗的食蟹猴的血压。静脉注射5 mg / kg时，明显的降压反应持续3个小时以上。

  DOI：

  10.1021/jm00160a049
• 作为产物：
  描述：

  对甲苯磺酰氯 、 N-Boc-L-组氨酸 在 sodium carbonate 作用下， 以 水 为溶剂， 反应 4.0h， 以46%的产率得到N-叔丁氧羰基-N(咪唑)-(4-甲基苯磺酰基)-L-组氨酸
  参考文献：
  名称：

  Activated ketone based inhibitors of human renin

  摘要：

  Application of the concept of activated ketones to the design of novel and potent transition-state analog inhibitors of the aspartyl protease renin is described. Three different classes of peptidic activated ketones were synthesized: 1,1,1-trifluoromethyl ketones, alpha-keto esters, and alpha-diketones. The corresponding alcohols were also evaluated as renin inhibitors in each series. While the trifluoromethyl alcohol 12 (I50 = 4000 nM) was equipotent to the simple methyl alcohol 7 (I50 = 3200 nM), the structurally similar alpha-hydroxy esters (32 and 30, I50's = 5.3 and 4.7 nM, respectively) and alpha-hydroxy ketones (41 and 42, I50 = 23 and 15 nM, respectively) were 150-300-fold more active. The hydrating capability of the activated ketone functionality was important for intrinsic potency in the case of trifluoromethyl ketones, as illustrated by the significantly better activity of trifluoromethyl ketone 13 (I50 = 250 nM) compared to its alcohol analog 12 (I50 = 4000 nM). It was however unimportant for the alpha-keto ester (20 and 31, I50 = 15 and 4.1 nM, respectively) and alpha-diketone (43 and 44, I50 = 52 and 28 nM, respectively) based inhibitors, since their activity was essentially similar to that of the corresponding alcohols. These results collectively suggest that, whereas the trifluoromethyl ketones derive their renin inhibitory potency primarily from their ability to become hydrated, this is not a critical feature for the activity of alpha-dicarbonyl-based inhibitors. The alpha-keto ester and alpha-diketone based renin inhibitors benefit predominantly from the hydrophobic and/or H-bonding type binding interactions of the neighboring ester or acyl group itself, rather than the ability of this group to deactivate the adjacent ketone group and thereby make it susceptible to hydration.

  DOI：

  10.1021/jm00069a001

文献信息

• Neurokinin B Analogs Substituted with Glycine
  作者：Tadashi Hashimoto、Tadashi Moro、Yoshiki Uchida

  DOI：10.1246/bcsj.59.4006

  日期：1986.12

  Four Neurokinin B analogs substituted with glycine at position 4, 5, 6, or 7 were synthesized by Merrifield’s solid phase method. Pharmacological property of the analogs is described. The results suggest that Phe6 and Val7 residues may be essential for intrinsic activity on smooth muscle.

  通过梅里菲尔德的固相合成法，合成了四种在第4、5、6或7位上用甘氨酸替代的神经激肽B类似物。描述了这些类似物的药理学特性。结果表明，苯丙氨酸6和缬氨酸7残基可能是平滑肌内源性活性的关键。
• Zn2+-Complexation by aβ-Peptidic Helix and Hairpin Containingβ3hCys andβ3hHis Building Blocks: Evidence from CD Measurements. Preliminary Communication
  作者：Francesco Rossi、Gérald Lelais、Dieter Seebach

  DOI：10.1002/hlca.200390215

  日期：2003.7

  the formation of a hairpin secondary structure. A β-decapeptide (3) has been designed to fold to a 314-helical secondary structure with neighboring His side chains in 6- and 9-positions. Circular-dichroism (CD) measurements show the capability of both peptides to bind Zn2+ ions in aqueous solution. In the case of the β-octapeptide, binding of Zn2+ causes a dramatic change of the CD spectrum, indicating

  两个新的β 3 -homohistidine-和β 3的含高半胱氨酸β -肽已经制备通过固相合成。甲β -octapeptide（2）包含七个β 3 -氨基酸和一个β 2 -氨基酸。的β 2 / β 3段已被放置在该肽的中间，其包含β 3 -氨基交替构造的酸，以诱导发夹二级结构的形成。甲β -decapeptide（3）已被设计为折叠成314螺旋二级结构，相邻的His侧链在6位和9位。圆二色性（CD）测量显示两种肽结合水溶液中Zn 2+离子的能力。在β-八肽的情况下，Zn 2+的结合引起CD光谱的急剧变化，表明其二级结构发生变化或稳定。Zn 2+离子在中性和碱性溶液中均能明显稳定β-十肽的3 14-螺旋。两个新的施工β -肽，我们需要有一个供应β -氨基甲酸衍生物的Fmoc- β 3hCys（TRT）-OH和的Fmoc- β 3 hHis（TRT）-OH，将其制备在本文中描述。
• A microwave enhanced cross-metathesis approach to peptidomimetics
  作者：Thomas Morris、David Sandham、Stephen Caddick

  DOI：10.1039/b700804j

  日期：——

  Functionalization of amino acid C- and N-termini with appropriate olefinic moieties allows for the generation of a peptidomimetic via a stereoselective cross-metathesis.

  用适当的烯烃部分对氨基酸C-和N-末端进行官能化可以通过立体选择性交叉复分解产生拟肽。
• Progress toward the assembly of the bicyclic theonellamide skeleton
  作者：Jyoti P. Mukherjee、Joyeeta Roy、Chyree S. Batton、Saroj Yadav、Douglas Wong、Carol M. Taylor

  DOI：10.1016/j.tet.2020.131127

  日期：2020.4

  synthesized in solution. Each ring was formed independently, providing insights into protecting group limitations, side reactions, and the optimal order of events to approach the formation of the bicyclic system. Ultimately, an undecapeptide was prepared, with the eastern ring formed. The twelfth amino acid, an l-α-aminoadipic acid building block, was prepared and preliminary investigations into its attachment

  的正交保护的τ-histidinoalanine残余物通过旋光纯的Boc-的区域选择性烷基化，合成升与亲电子从的Fmoc-衍生的磺酰胺酯-His-OTCE（TCE =三氯乙基）d -Ser-OBn的 目的是合成一种非天然的theonellamide，并调用其他10个氨基酸的易于获得的变体。在溶液中合成了与“ theonellamide X”的东环和西环相对应的肽片段。每个环都是独立形成的，可深入了解保护基团的限制，副反应以及接近双环系统形成的最佳事件顺序。最终，制备了十一肽，形成了东环。第十二氨基酸，升制备了-α-氨基己二酸构件，并报道了其与十一肽的连接的初步研究。
• Chemical synthesis and adjuvant activity of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) analogs.
  作者：KEIICHI KAMISANGO、IKUO SAIKI、YOSHIRO TANIO、SHIGERU KOBAYASHI、TSUNEHIKO FUKUDA、ISAO SEKIKAWA、ICHIRO AZUMA、YUICHI YAMAMURA

  DOI：10.1248/cpb.29.1644

  日期：——

  Twenty-two kinds of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) analogs were synthesized and their adjuvant activity on the induction of delayed-type hypersensitivity to ABA-N-acetyl-L-tyrosine was examined. The L-alanine residue of MDP could be replaced with certain other amino acid residues without loss of activity. The structureactivity relationship of these compounds is discussed. With respect to replacement of the L-alanine residue of MDP in connection with adjuvant activity, it was shown that (1) amino acids having a suitable side chain were effective, (2) basic amino acids were unfavorable, (3) aromatic amino acids were unfavorable, and (4) acidic amino acids were effective. The D-isoglutamine residue of MDP was considered to be essential for the adjuvant activity. The adjuvant activity was decreased by esterification with methanol of the D-glutamic acid residue of MDP and related N-acetylmuramyldipeptides, but the adjuvant activity of D-glutamic acid diamide analogs was similar to that of MDP and its analogs.

  合成了二十二种N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺(MDP)的类似物,并检验了它们对诱导对ABA＿N-乙酰-L-酪氨酸的迟发型过敏反应的佐剂活性。MDP的L-丙氨酸残基能为某些其他氨基酸残基所置换,而活性不变。讨论了这些化合物的结构-活性关系。关于MDP中L-丙氨酸残基的置换和佐剂活性,表明; (1)具有合适侧链的氨基酸是有效的; (2)碱性氨基酸不是有利的; (3)芳香族的氨基酸不是有利的; (4)酸性氨基酸是有效的。认为MDP的D-异谷氨酰胺残基对佐剂活性是必要的。与MDP和有关N-乙酰胞壁酰二肽的D-谷氨酸残基的酯化作用使佐剂活性降低,但D-谷氨酸二酰胺类似物的佐剂活性与MDP及其类似物的佐剂活性相似。