N-Cbz-正亮氨醛 | 109364-33-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-Cbz-正亮氨醛
• 中文别名: (S)-2-苄氧羰基氨基正己醛
• 英文名称: N-(benzyloxycarbonyl)-L-norleucinal
• 英文别名: (S)-1-oxohexane-2-benzylcarbamate；((S)-1-Formyl-pentyl)-carbamic acid benzyl ester；benzyl N-[(2S)-1-oxohexan-2-yl]carbamate
• CAS: 109364-33-2
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: MVYMZCOVLGBDRV-ZDUSSCGKSA-N

物化性质

• 沸点：
  386.2±35.0 °C(Predicted)
• 密度：
  1.077±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-Cbz-正亮氨醛 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 (3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide
  参考文献：
  名称：

  Design of small molecule ketoamide-based inhibitors of cathepsin K

  摘要：

  A novel series of ketoamide-based inhibitors of cathepsin K has been identified. Modifications to p(2) and p(3) elements were crucial to enhancing inhibitory activity. Although not optimized, a selected inhibitor was effective in attenuating type 1 collagen hydrolysis in a surrogate assay of bone resorption. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.029
• 作为产物：
  描述：

  benzyl N-[(2S)-1-[methoxy(methyl)amino]-1-oxohexan-2-yl]carbamate 生成 N-Cbz-正亮氨醛
  参考文献：
  名称：

  RODRIGUEZ, M.;LIGNON, M. -F.;GALAS, M. -CH.;FULCRAND, P.;MENDRE, CH.;AUME+, J. MED. CHEM., 30,(1987) N 8, 1366-1373

  摘要：

  DOI：

文献信息

• Addition of Allylic Metals to α-Aminoaldehydes. Application to the Synthesis of Statine, Ketomethylene and Hydroxyethylene Dipeptide Isosteres
  作者：J.V.N. Vara Prasad、Daniel H. Rich

  DOI：10.1016/s0040-4039(00)98790-2

  日期：1990.1

  A general and stereoselective method to statine, ketomethylene and hydroxyethylene dipeptide isosteres is described. The key reaction is the diastereoselective allyl metal addition to α-aminoaldehydes.

  描述了对他汀类，酮亚甲基和羟乙烯二肽等排体的一般和立体选择方法。关键反应是将非对映选择性烯丙基金属加到α-氨基醛中。
• Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties
  作者：Jordi Calveras、Meritxell Egido-Gabás、Livia Gómez、Josefina Casas、Teodor Parella、Jesús Joglar、Jordi Bujons、Pere Clapés

  DOI：10.1002/chem.200900838

  日期：2009.7.27

  The polyhydroxylated pyrrolidines generated were tested as inhibitors against seven glycosidases. Among them, good inhibitors of α‐L‐fucosidase (IC50=1–20 μM), moderate of α‐L‐rhamnosidase (IC50=7–150 μM), and weak of α‐D‐mannosidase (IC50=80–400 μM) were identified. The apparent inhibition constant values (Ki) were calculated for the most relevant inhibitors and computational docking studies were

  据报道，通过DHAP醛缩酶的催化，醛醇将磷酸二羟基丙酮磷酸酯（DHAP）加成到C-α-取代的N -Cbz-2-氨基醛衍生物上而生成的吡咯烷型亚氨基糖的化学酶法合成。来自大肠杆菌的L-藻糖-1-磷酸醛缩酶（FucA）和L-鼠李糖-1磷酸醛缩酶（RhuA）用作生物催化剂以在亚氨基糖上产生构型多样性。FucA催化剂可很好地耐受C-α处的烷基线性取代（即40-70％转化为醛醇加合物），而除二甲基和苄基取代（20％）外，未观察到具有C-α-烷基支链取代的产物。 。RhuA是用途最广泛的生物催化剂：C-α-烷基直链基团转化为羟醛加成物的转化率最高（60-99％），而C-α-烷基支链基团的转化率中等至良好（50-80％），二甲基和苄基取代基（20％）除外。FucA是最具立体选择性的生物催化剂（90％至100％的抗（3 R，4 R）加合物）。RhuA对（S）-N具有高度立体选择性-Cbz -2-氨基醛（90-100％顺式（即，3
• Highly efficient aldol additions of DHA and DHAP to N-Cbz-amino aldehydes catalyzed by l-rhamnulose-1-phosphate and l-fuculose-1-phosphate aldolases in aqueous borate buffer
  作者：Xavier Garrabou、Jordi Calveras、Jesús Joglar、Teodor Parella、Jordi Bujons、Pere Clapés

  DOI：10.1039/c1ob06263h

  日期：——

  Aldol addition reactions of dihydroxyacetone (DHA) to N-Cbz-amino aldehydes catalyzed by L-rhamnulose-1-phosphate aldolase (RhuA) in the presence of borate buffer are reported. High yields of aldol adduct (e.g. 70–90%) were achieved with excellent (>98 : 2 syn/anti) stereoselectivity for most S or R configured acceptors, which compares favorably to the reactions performed with DHAP. The stereochemical outcome was different and depended on the N-Cbz-amino aldehyde enantiomer: the S acceptors gave the syn (3R,4S) aldol adduct whereas the R ones gave the anti (3R,4R) diastereomer. Moreover, the tactical use of Cbz protecting group allows simple and efficient elimination of borate and excess of DHA by reverse phase column chromatography or even by simple extraction. This, in addition to the use of unphosphorylated donor nucleophile, makes a useful and expedient methodology for the synthesis of structurally diverse iminocyclitols. The performance of aldol additions of dihydroxyacetone phosphate (DHAP) to N-Cbz-amino aldehydes using RhuA and L-fuculose-1-phosphate aldolase (FucA) catalyst in borate buffer was also evaluated. For FucA catalysts, including FucA F131A, the initial velocity of the aldol addition reactions using DHAP were between 2 and 10 times faster and the yields between 1.5 and 4 times higher than those in triethanolamine buffer. In this case, the retroaldol velocities measured for some aldol adducts were lower than those without borate buffer indicating some trapping effect that could explain the improvement of yields.

  报告了二羟基丙酮（DHA）与N-Cbz-氨基醛的 aldol 加成反应，该反应是在硼酸盐缓冲液存在下，由 L-鼠李糖-1-磷酸 aldol 酶（RhuA）催化进行的。大部分 S或 R 配置的受体都可以以高产率（例如 70–90%）获得 aldol 加合物，并具有优异的立体选择性（>98 : 2 syn/anti），这与使用 DHAP 进行的反应相比表现良好。立体化学结果不同，依赖于 N-Cbz-氨基醛的对映异构体：S 受体产生 syn（3R,4S）aldol 加合物，而 R 受体则产生 anti（3R,4R）联体异构体。此外，策略性地使用 Cbz 保护基团使得通过反相色谱或简单提取可以简单高效地去除硼酸盐和多余的 DHA。这一点，加上使用未磷酸化的供体亲核试剂，使得合成结构多样性免疫环醇的方法更为实用和高效。同时，评估了使用 RhuA 和 L-岩藻糖-1-磷酸 aldol 酶（FucA）催化剂在硼酸盐缓冲液中对 N-Cbz-氨基醛进行二羟基丙酮磷酸盐（DHAP）进行的 aldol 加成反应的表现。对于 FucA 催化剂（包括 FucA F131A），使用 DHAP 的 aldol 加成反应的初始速率是三乙醇胺缓冲液中反应的 2 到 10 倍，产率高出 1.5 到 4 倍。在这种情况下，测得某些 aldol 加合物的逆 aldol 速率低于不含硼酸盐缓冲液的情况，这表明存在某种捕获效应，可以解释产率的提高。
• Synthesis and biological activities of pseudopeptide analogs of the C-terminal heptapeptide of cholecystokinin. On the importance of the peptide bonds
  作者：Marc Rodriguez、Marie Francoise Lignon、Marie Christine Galas、Pierre Fulcrand、Christiane Mendre、Andre Aumelas、Jeanine Laur、Jean Martinez

  DOI：10.1021/jm00391a017

  日期：1987.8

  A series of pseudopeptide analogues of the C-terminal heptapeptide of cholecystokinin in which each peptide bond, one at a time, has been replaced by a CH2NH bond were synthesized: Z-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp psi-(CH2NH)Phe-NH2 (1), Z-Tyr(SO3-)-Nle-Gly-Trp-Nle psi (CH2NH)Asp-Phe-NH2 (2), Z-Tyr(SO3-)-Nle-Gly-Trp psi-(CH2NH)Nle-Asp-Phe-NH2 (3), Z-Tyr(SO3-)-Nle-Gly psi(CH2NH)Trp-Nle-Asp-Phe-NH2 (4)

  合成了胆囊收缩素C端七肽的一系列伪肽类似物，其中每个肽键一次被一个CH2NH键取代：Z-Tyr（SO3-）-Nle-Gly-Trp-Nle- Asp psi-（CH2NH）Phe-NH2（1），Z-Tyr（SO3-）-Nle-Gly-Trp-Nle psi（CH2NH）Asp-Phe-NH2（2），Z-Tyr（SO3-）-Nle -Gly-Trp psi-（CH2NH）Nle-Asp-Phe-NH2（3），Z-Tyr（SO3-）-Nle-Gly psi（CH2NH）Trp-Nle-Asp-Phe-NH2（4），Z- Tyr（SO3-）-Nle psi-（CH2NH）Gly-Trp-Nle-Asp-Phe-NH2（5），Z-Tyr（SO3-）-Met-Gly-Trp-Nle-Asp psi（CH2NH）Phe- NH2（6），Z-Tyr-（SO3-）-Met-Gly-Trp-Nle psi（
• [EN] ALPHA-KETOAMIDE DERIVATIVES AS CATHEPSIN K INHIBITORS<br/>[FR] DERIVES D'ALPHA-CETOAMIDE UTILISES EN TANT QU'INHIBITEURS DE LA CATHEPSINE K
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2003013518A1

  公开（公告）日：2003-02-20

  Biaryl ketoamide derivatives (I), which are useful as cathepsin K inhibitors are described herein. The described invention also includes methods of making such biaryl ketoamide derivatives as well as methods of using the same in the treatment of disorders, including osteoporosis, associated with enhanced bone turnover which can ultimately lead to fracture.

  本文描述了有用于作为蛋白酶K抑制剂的双芳基酮酰胺衍生物(I)。所述的发明还包括制备这种双芳基酮酰胺衍生物的方法，以及在治疗与增强骨转换相关的疾病，包括骨质疏松症，最终可能导致骨折的方法。