Boc-(3R,4S)-statine ethyl ester | 67010-44-0

• 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-(3R,4S)-statine ethyl ester
• 英文别名: (3R,4S)-4-(N-Boc-amino)-3-hydrohy-6-methylheptanoic acid ethyl ester；ethyl (3R,4S)-Boc-4-amino-3-hydroxy-6-methylheptanoate；N^α-Boc-(3R,4S)-Sta-OEt；(3R0)-N-Boc-statine ethyl ester；(3R,4S)-(t-butyloxycarbonyl)-4-amino-3-hydroxy-6-methylheptanoic acid ethyl ester；(3R,4S)-ethyl 4-(tert-butoxycarbonylamino)-3-hydroxy-6-methylheptanoate；(3R,4S)-(t-butyloxycarbonyl)-statine ethyl ester；ethyl (3R,4S)-3-hydroxy-6-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]heptanoate
• CAS: 67010-44-0
• 化学式: C₁₅H₂₉NO₅
• 分子量: 303.399
• InChiKey: QPPGGDLXGCHWBS-NWDGAFQWSA-N

物化性质

• 熔点：
  48-50 °C
• 沸点：
  422.3±35.0 °C(Predicted)
• 密度：
  1.044±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-(3R,4S)-statine ethyl ester 在 sodium hydroxide 、 双氧水 、 二异丁基氢化铝 、 sodium thiosulfate 、 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 40.25h， 生成 5(R)-5-<1(S)-1-(N-Boc-amino)-3-methylbutyl>dihydrofuran-2(3H)-one
  参考文献：
  名称：

  A short, stereoselective synthesis of the lactone precursor to 2R,4S,5S hydroxyethylene dipeptide isosteres

  摘要：

  DOI：

  10.1021/jo00375a014
• 作为产物：
  描述：

  BOC-L-亮氨酸 生成 Boc-(3R,4S)-statine ethyl ester
  参考文献：
  名称：

  Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal Nin-For-Trp (Ftr): angiotensinogen congeners modified by P1-P1' Phe-Phe, Sta, Leu.psi.[CH(OH)CH2]Val or Leu.psi.[CH2NH]Val substitutions

  摘要：

  A structure-conformation-activity investigation of several angiotensinogen (ANG) based inhibitors of human renin modified by either Phe-Phe, Sta, Leu psi[CH2NH]Val, or Leu psi[CH(OH)CH2]Val at the P1-P1' clevage site and P5 Trp(Nin-For) (Ftr) was performed. Specifically, Ac-Ftr-Pro-Phe-His-Phe-Phe-Val-Ftr-NH2 (1) provided a potent (KI = 2.7 X 10(-8) M) P1-P1' Phe-Phe substituted renin inhibitor to initiate these studies. Substitution of the P1-P1' Phe-Phe in compound 1 by Sta effected a 1,000-fold increase in biological potency for the resultant octapeptide Ac-Ftr-Pro-Phe-His-Sta-Val-Ftr-NH2 (10; KI = 6.7 X 10(-11) M). Kinetic analysis of compound 10 showed it to be a competitive inhibitor of human renin catalyzed proteolysis of human ANG. Chemical modifications of the compounds 1 and 10 were evaluated on the basis of comparative human plasma renin inhibitory activities (IC50 values) in vitro. Carboxy-terminal truncation studies on compound 10 showed that the P2' Val and P3' Ftr residues could both be eliminated without significant loss (ca. 10-fold) in renin inhibitory activity as exemplified by the pentapeptide Ac-Ftr-Pro-Phe-His-Sta-NH2 (12; IC50 = 3.8 X 10(-9) M). In addition, the corresponding P1-P1' Leu psi[CH(OH)CH2]Val and Leu psi[CH2NH]Val derivatives of compound 12 were potent renin inhibitors: Ac-Ftr-Pro-Phe-His-Leu psi[CH(OH)CH2]Val-NH2 (13; IC50 = 3.1 X 10(-10) M) and Ac-Ftr-Pro-Phe-His-Leu psi[CH2NH]Val-NH2 (14; IC50 = 2.1 X 10(-8) M). The structure-conformation-activity properties of the N-terminal Ftr substitution of these human renin inhibitors was examined by (1) comparative analysis of several analogues of 1 and Ac-Ftr-Pro-Phe-His-Sta-Ile-NH2 (17; IC50 = 1.0 X 10(-10) M) having P5 site modifications by Trp, His, D-Ftr, and D-His, (2) deletion of the N-terminal Ftr residue from compounds 12 and 17, to provide Ac-Pro-Phe-His-Sta-Ile-NH2 (16; IC50 = 3.1 X 10(-8) M) and Ac-Pro-Phe-His-Sta-NH2 (15; IC50 = 5.6 X 10(-6) M), and (3) computer modeling and dynamics studies of compounds 1 and 17 bound to CKH-RENIN, a simulated human renin model, which were focused on identifying potential intermolecular interactions of their common P5-P2 sequence, Ac-Ftr-Pro-Phe-His, at the enzyme active site.(ABSTRACT TRUNCATED AT 400 WORDS)

  DOI：

  10.1021/jm00396a006

文献信息

• Synthesis of β‐Secretase Inhibitors Containing a Hydroxyethylene Dipeptide Isostere
  作者：Xiaoming Yang、Xiaomin Zou、Yiqiu Fu、Ke Mou、Gang Fu、Chao Ma、Ping Xu

  DOI：10.1080/00397910600977509

  日期：2007.1.1

  Abstract β‐Secretase inhibitors with a Leu*Ala hydroxyethylene dipeptide (HED) isostere have been an especially interesting topic in recent years. In this study, a template compound 17 was synthesized, featuring truncation at the P2′ position and changes at P2 and P3, which differs from other reported potent inhibitors. The purpose was to explore optimal reaction conditions and construct an inhibitor

  摘要 近年来，具有 Leu*Ala 羟基乙烯二肽 (HED) 等排体的 β-分泌酶抑制剂一直是一个特别有趣的话题。本研究合成了模板化合物17，其P2'位置截断，P2和P3发生变化，与其他报道的强效抑制剂不同。目的是探索最佳反应条件并构建抑制剂库以研究理想的蛋白质-底物相互作用。
• Exploring β-Hydroxy γ-Amino Acids (Statines) in the Design of Hybrid Peptide Foldamers
  作者：Anupam Bandyopadhyay、Ankita Malik、Mothukuri Ganesh Kumar、Hosahudya N. Gopi

  DOI：10.1021/ol403290h

  日期：2014.1.3

  The synthesis and characterization of syn and anti β-hydroxy γ-amino acid (statine) diastereoisomers, their utilization in the design of hybrid peptide foldamers, and their single crystal conformations are studied.

  研究了顺式和反式β-羟基γ-氨基酸（他汀类）非对映异构体的合成与表征，在杂合肽折叠剂设计中的应用，以及它们的单晶构象。
• isostatine衍生物及其制备方法
  申请人：新昌县大成生物科技有限公司

  公开号：CN104744307B

  公开（公告）日：2017-01-04

  本发明公开了一种isostatine衍生物及其制备方法，本发明的方法采用摩尔比2‑4:1的二乙基锌和四氯化锡混合物作为催化剂，提高了反应温度和产率，更适合工业化生产。
• A facile synthesis of statine and analogs by reduction of .beta.-keto esters derived from Boc-protected amino acids. HPLC analyses of their enantiomeric purity
  作者：Juergen Maibaum、Daniel H. Rich

  DOI：10.1021/jo00239a035

  日期：1988.2
• Potent and selective inhibitors of an aspartyl protease-like endothelin converting enzyme identified in rat lung
  作者：Kazumi Shiosaki、Andrew S. Tasker、Gerard M. Sullivan、Bryan K. Sorensen、Thomas W. von Geldern、Jinshyun R. Wu-Wong、Carol A. Marselle、Terry J. Opgenorth

  DOI：10.1021/jm00056a007

  日期：1993.2

  Two structurally distinct series of potent and selective inhibitors of an aspartyl protease-like endothelin converting enzyme (ECE) activity identified in the rat lung have been developed. Pepstatin A, which potently inhibits the rat lung ECE, served as the basis for the first series. Alternatively, selected renin inhibitors containing the dihydroxyethylene moiety were shown to be inhibitors of rat lung activity. Subsequent modifications improved inhibition of the rat lung ECE while eliminating renin activity. Both series of ECE inhibitors demonstrated a range of selectivity over Cathepsin D. Water-solubilizing moieties were appended onto selected compounds to facilitate in vivo testing. Partial reduction of the pressor response to exogenously administered Big ET-1 was observed with selected rat lung ECE inhibitors.