Boc-(R)-β³-HValΨ[CSNH]-(S)-β³-HAla-OH | 261722-53-6

• 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: Boc-(R)-β³-HValΨ[CSNH]-(S)-β³-HAla-OH
• 英文别名: Boc-β³hValΨ[CSNH]-β³hAla-OH；(3S)-3-[[(3R)-4-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]pentanethioyl]amino]butanoic acid
• CAS: 261722-53-6
• 化学式: C₁₅H₂₈N₂O₄S
• 分子量: 332.464
• InChiKey: LLNVKCDRQSCWQY-WDEREUQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-(R)-β³-HValΨ[CSNH]-(S)-β³-HAla-OH 在 劳森试剂 、 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 水 为溶剂， 反应 69.0h， 生成 Boc-(R)-β³-HValΨ[CSNH]-(S)-β³-HAlaΨ[CSNH]-(S)-β³-HLeuΨ[CSNH]-(R)-β³-HVal-(S)-β³-HAla-(S)-β³-HLeu-OH
  参考文献：
  名称：

  β-Thiopeptides: Synthesis, NMR Solution Structure, CD Spectra, and Photochemistry

  摘要：

  To test the effect of NH-C=S groups (Scheme 1) on the stability of beta-peptide secondary structures, we have synthesized three beta-thiohexapeptide analogues of H-(beta-HVal-beta-HAla-beta-HLeu)(2)-OH (1) with one, two, and three C=S groups in the N-terminal positions (cf. 2-4 and model in Fig. 1). The first C=S group was introduced selectively by treatment with Lawesson reagent of Boc-beta-dipeptide esters (6 and 8). A series of fragment-coupling steps(with reagents as for the corresponding sulfur-free building blocks) and another thionation reaction led to the title compounds with a C=S group in residues 1, 1, and 3, as well as 1, 2, and 3 of the beta-hexapeptide (Schemes 2 and 3). The sulfur derivatives, especially those with three C=S groups, were much more soluble in organic media than the sulfur-free analogues (> 1000-fold in CHCl3; Table 1). The UV and CD spectra (in CHCl3, MeOH, and H2O) of the new compounds were recorded and compared with those of the parent beta-hexapeptide 1 (Figs. 2-4); they indicate the presence of more than one secondary structure under the various conditions. Most striking is a pronounced exciton splitting (Delta lambda ca. 20 nm, amplitude up to +121000) of the pi pi*(C=S) band near 270 nm with the beta-trithiohexapeptide (with and without terminal protecting groups),and strong, so-called 'primary solvent effects', in the CD spectra. The CD spectrum of the beta-dithiohexapeptide 3 undergoes drastic changes upon irradiation with 266-nm laser light of a MeOH solution (Fig. 5). The NMR structure in CD3OH of the unprotected beta-trithiohexapeptide 4 was determined to be an (M)-3(14)-helix (Fig. 7), very similar to that of the non-thionated analogue (cf. 1). NMR and mass spectra of the beta-hexapeptides with C=S and with C=O groups are compared (Figs. 6 and 8).

  DOI：

  10.1002/(sici)1522-2675(19991215)82:12<2067::aid-hlca2067>3.0.co;2-5
• 作为产物：
  描述：

  Boc-(R)-β³-HVal-(S)-β³-HAla-OMe 在 劳森试剂 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 7.5h， 生成 Boc-(R)-β³-HValΨ[CSNH]-(S)-β³-HAla-OH
  参考文献：
  名称：

  β-Thiopeptides: Synthesis, NMR Solution Structure, CD Spectra, and Photochemistry

  摘要：

  To test the effect of NH-C=S groups (Scheme 1) on the stability of beta-peptide secondary structures, we have synthesized three beta-thiohexapeptide analogues of H-(beta-HVal-beta-HAla-beta-HLeu)(2)-OH (1) with one, two, and three C=S groups in the N-terminal positions (cf. 2-4 and model in Fig. 1). The first C=S group was introduced selectively by treatment with Lawesson reagent of Boc-beta-dipeptide esters (6 and 8). A series of fragment-coupling steps(with reagents as for the corresponding sulfur-free building blocks) and another thionation reaction led to the title compounds with a C=S group in residues 1, 1, and 3, as well as 1, 2, and 3 of the beta-hexapeptide (Schemes 2 and 3). The sulfur derivatives, especially those with three C=S groups, were much more soluble in organic media than the sulfur-free analogues (> 1000-fold in CHCl3; Table 1). The UV and CD spectra (in CHCl3, MeOH, and H2O) of the new compounds were recorded and compared with those of the parent beta-hexapeptide 1 (Figs. 2-4); they indicate the presence of more than one secondary structure under the various conditions. Most striking is a pronounced exciton splitting (Delta lambda ca. 20 nm, amplitude up to +121000) of the pi pi*(C=S) band near 270 nm with the beta-trithiohexapeptide (with and without terminal protecting groups),and strong, so-called 'primary solvent effects', in the CD spectra. The CD spectrum of the beta-dithiohexapeptide 3 undergoes drastic changes upon irradiation with 266-nm laser light of a MeOH solution (Fig. 5). The NMR structure in CD3OH of the unprotected beta-trithiohexapeptide 4 was determined to be an (M)-3(14)-helix (Fig. 7), very similar to that of the non-thionated analogue (cf. 1). NMR and mass spectra of the beta-hexapeptides with C=S and with C=O groups are compared (Figs. 6 and 8).

  DOI：

  10.1002/(sici)1522-2675(19991215)82:12<2067::aid-hlca2067>3.0.co;2-5

文献信息

• β- and γ-Di- and Tripeptides as Potential Substrates for the Oligopeptide Transporter hPepT1
  作者：Ina Hubatsch、Per I. Arvidsson、Dieter Seebach、Kristina Luthman、Per Artursson

  DOI：10.1021/jm070148u

  日期：2007.10.1

  The hPepT1-mediated transport properties of a series of 11 synthesized beta- and gamma-peptides have been studied in Caco-2 cells. The results show that several of the compounds interact with the peptide transporter, but only two beta-dipeptides act as substrates and are transported across the cell monolayers. These two are less-efficient substrates than alpha-peptides. Larger derivatives than beta-dipeptides do not act as hPepT1 substrates, but instead, they appear to be substrates for P-glycoprotein efflux.
• β-Thiopeptides: Synthesis, NMR Solution Structure, CD Spectra, and Photochemistry
  作者：Thierry Sifferlen、Magnus Rueping、Karl Gademann、Bernhard Jaun、Dieter Seebach

  DOI：10.1002/(sici)1522-2675(19991215)82:12<2067::aid-hlca2067>3.0.co;2-5

  日期：1999.12.15

  To test the effect of NH-C=S groups (Scheme 1) on the stability of beta-peptide secondary structures, we have synthesized three beta-thiohexapeptide analogues of H-(beta-HVal-beta-HAla-beta-HLeu)(2)-OH (1) with one, two, and three C=S groups in the N-terminal positions (cf. 2-4 and model in Fig. 1). The first C=S group was introduced selectively by treatment with Lawesson reagent of Boc-beta-dipeptide esters (6 and 8). A series of fragment-coupling steps(with reagents as for the corresponding sulfur-free building blocks) and another thionation reaction led to the title compounds with a C=S group in residues 1, 1, and 3, as well as 1, 2, and 3 of the beta-hexapeptide (Schemes 2 and 3). The sulfur derivatives, especially those with three C=S groups, were much more soluble in organic media than the sulfur-free analogues (> 1000-fold in CHCl3; Table 1). The UV and CD spectra (in CHCl3, MeOH, and H2O) of the new compounds were recorded and compared with those of the parent beta-hexapeptide 1 (Figs. 2-4); they indicate the presence of more than one secondary structure under the various conditions. Most striking is a pronounced exciton splitting (Delta lambda ca. 20 nm, amplitude up to +121000) of the pi pi*(C=S) band near 270 nm with the beta-trithiohexapeptide (with and without terminal protecting groups),and strong, so-called 'primary solvent effects', in the CD spectra. The CD spectrum of the beta-dithiohexapeptide 3 undergoes drastic changes upon irradiation with 266-nm laser light of a MeOH solution (Fig. 5). The NMR structure in CD3OH of the unprotected beta-trithiohexapeptide 4 was determined to be an (M)-3(14)-helix (Fig. 7), very similar to that of the non-thionated analogue (cf. 1). NMR and mass spectra of the beta-hexapeptides with C=S and with C=O groups are compared (Figs. 6 and 8).