(S)-2-<(tert-Butoxycarbonyl)amino>-3-phenylpropyl thioacetate | 122818-32-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-2-<(tert-Butoxycarbonyl)amino>-3-phenylpropyl thioacetate
• 英文别名: (S) 1-thio-S-acetyl-2-amino-N-(tert-butyloxycarbonyl)-3-phenyl-propane；(S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl thioacetate；S-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropyl] ethanethioate
• CAS: 122818-32-0
• 化学式: C₁₆H₂₃NO₃S
• 分子量: 309.43
• InChiKey: FNQGVRYQUMZRGM-AWEZNQCLSA-N

物化性质

• 沸点：
  443.9±45.0 °C(Predicted)
• 密度：
  1.112±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  N-Boc-L-苯丙氨醇	(S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol	66605-57-0	C14H21NO3	251.326
  BOC-L-苯丙氨酸	N-tert-butoxycarbonyl-L-phenylalanine	13734-34-4	C14H19NO4	265.309
  S)-2-(叔丁氧羰基氨基)-3-苯基丙基甲烷磺酸盐	(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl methanesulfonate	109687-66-3	C15H23NO5S	329.417

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  (S)-2-苄基-2-n-boc氨基乙基硫醇	(S)-tert-butyl (1-mercapto-3-phenylpropan-2-yl)carbamate	141437-85-6	C14H21NO2S	267.392
  ——	1,1-Dimethylethyl N-[(1S)-1-[(chlorosulfinyl)methyl]-2-phenylethyl]carbamate	145641-39-0	C14H20ClNO3S	317.837
  ——	(S)-2-(acetylamino)-3-phenylpropyl thioacetate	676457-72-0	C13H17NO2S	251.349
  ——	Thioacetic acid S-((S)-2-amino-3-phenyl-propyl) ester	118079-35-9	C11H15NOS	209.312

反应信息

• 作为反应物：
  描述：

  (S)-2-<(tert-Butoxycarbonyl)amino>-3-phenylpropyl thioacetate 在 哌啶 、 N-甲基吗啉 、 吡啶 、 N-甲基吡咯烷酮 、 四氧化锇 、 磺酰氯 、 乙酸酐 、 N-甲基吗啉氧化物 、 三乙胺 、 2,6-二氯苯甲酰氯 、 Tentagel resin 作用下， 生成 ((S)-2-tert-Butoxycarbonylamino-3-phenyl-propane-1-sulfonylamino)-acetic acid methyl ester
  参考文献：
  名称：

  Molecular diversity of peptidomimetics: Approaches to the solid-phase synthesis of peptidosulfonamides

  摘要：

  In order to use the potential molecular diversity of the peptidosulfonamide peptidomimetics ultimately in libraries, approaches towards the solid-phase synthesis of peptidosulfonamides are a prerequisite. It is shown that peptidosulfonamides can be synthesized by solid-phase synthesis methods using either a Merrifield or a Tentagel(R) resin. Better and more reproducible results are obtained using the latter resin. The possibility to prepare cyclic peptidosulfonamides was illustrated by the synthesis of cyclo-phenylalanyl Psi [CH2S(O)(2)N]-glycine. However, translation of synthesis of peptidosulfonamides in solution to a solid-phase method was rather laborious and still requires careful optimization. Copyright (C) 1996 Elsevier Science Ltd.

  DOI：

  10.1016/0968-0896(96)00061-2
• 作为产物：
  描述：

  ethoxycarbonyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoate 在 sodium tetrahydroborate 、 caesium carbonate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-<(tert-Butoxycarbonyl)amino>-3-phenylpropyl thioacetate
  参考文献：
  名称：

  Synthesis of Peptidosulfinamides and Peptidosulfonamides: Peptidomimetics Containing the Sulfinamide or Sulfonamide Transition-State Isostere

  摘要：

  Synthetic routes are described toward the preparation of alpha- as well as beta-substituted aminoethanesulfinyl chlorides, starting from either an aldehyde or from an amino acid derivative. The sulfinyl chlorides are used as building blocks for the preparation of homochiral alpha- or beta- substituted sulfinamide and sulfonamide transition-state isosteres. The methodology has been applied to the synthesis of peptidosulfonamide peptidomimetics such as a hapten needed for the generation of antibodies and potential HIV protease inhibitors. In addition, the beta-substituted aminoethanesulfinyl chlorides were used as building blocks for the preparation of a tetrapeptidosulfonamide, which can be considered as a biopolymer mimetic, employing a repetition of a cycle of three reactions: coupling of the sulfinyl chloride to the N-terminus of the growing peptidosulfonamide, oxidation to the sulfonamide, and deprotection of the N-terminus.

  DOI：

  10.1021/jo00121a038

文献信息

• Synthesis and evaluation of chloromethyl sulfoxides as a new class of selective irreversible cysteine protease inhibitors
  作者：Arwin J. Brouwer、Anton Bunschoten、Rob M.J. Liskamp

  DOI：10.1016/j.bmc.2007.07.045

  日期：2007.11

  The synthesis and biological evaluation of a new class of selective irreversible cysteine protease inhibitors is described. A set of amino acid based chloromethyl sulfoxides was prepared and they were found to inhibit irreversibly the cysteine protease papain. They were selective for cysteine proteases since no inhibition was found for the serine protease chymotrypsin.

  描述了新型的选择性不可逆半胱氨酸蛋白酶抑制剂的合成和生物学评估。制备了一套基于氨基酸的氯甲基亚砜，发现它们不可逆地抑制半胱氨酸蛋白酶木瓜蛋白酶。由于对丝氨酸蛋白酶胰凝乳蛋白酶没有抑制作用，因此它们对半胱氨酸蛋白酶具有选择性。
• Mixed-inhibitor-prodrug as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes
  作者：Marie Claude Fournie-Zaluski、Pascal Coric、Serge Turcaud、Evelyne Lucas、Florence Noble、Raphael Maldonado、Bernard P. Roques

  DOI：10.1021/jm00091a016

  日期：1992.6

  In order to evaluate the possible advantages of potentiating the effects of the endogenous enkephalins, to obtain analgesia without the serious drawbacks of morphine, it was essential to design systemically active compounds which inhibit the two metabolizing enzymes, aminopeptidase N (APN) and neutral endopeptidase 24.11 (NEP). A new concept combining the idea of "prodrug" and "mixed inhibitor" was therefore developed. Given the high efficiency of beta-mercaptoalkylamines as APN inhibitors and of N-(mercaptoacyl) amino acids as NEP inhibitors, compounds associating these molecules through disulfide or thioester bonds, which are known to increase lipophilicity and to favor passage across the blood-brain barrier, have been synthesized. An HPLC study indicated that the disulfide bridge was resistant to serum enzymes but was cleaved by brain membrane homogenates, suggesting that the active inhibitors were released in the central nervous system. The validity of the approach was verified by the efficient antinociceptive responses obtained in the hot plate test in mice after iv administration of disulfide-containing inhibitors (ED50s of from 4 to 26 mg/kg on the jump latency time). The analgesic potencies of the "mixed inhibitor-prodrug" RB 101 [H2NCH(CH2CH2SCH3)CH2SSCH2CH(CH2Ph)CONHCH(CH2Ph)COOCH2Ph] after iv administration were three times greater than those of a similar combined dose of its two constitutive moieties. The separation of the two diastereoisomers constituting RB 101 showed that the analgesia has a stereochemical dependence, the (S,S,S)-isomer being more active than the (S,R,S)-isomer. Furthermore, in the tail flick test in the rat, RB 101 gave 38% analgesia at a dose of 80 mg/kg. Due to its high efficiency and its longer pharmacological effect, RB 101 was selected for a complete study of its analgesic properties.
• Synthesis of peptides containing the β-substituted aminoethane sulfinamide or sulfonamide transition-state isostere derived from amino acids
  作者：Wilna J. Moree、Gijs A. van der Marel、Rob M.J. Liskamp

  DOI：10.1016/s0040-4039(00)60981-4

  日期：1992.10

  Alpha-amino acids can be converted to homochiral beta-substituted aminoethane sulfinamide or sulfonamide transition-state isosteres, which can be incorporated into peptides. These transition-state analogues e.g. the sulfonamide isostere of Phe-Phe will be used for the generation of catalytic antibodies as well as for the development of protease inhibitors.
• Inhibition of α-chymotrypsin with thiol-bearing substrate analogues in the presence of zinc ion
  作者：Min Su Han、Dong Ju Oh、Dong H. Kim

  DOI：10.1016/j.bmcl.2003.11.058

  日期：2004.2

  We have demonstrated that thiol-bearing analogues of alpha-chymotrysin (alpha-CT) substrates such as (S)-(1-benzyl-2-thiolethyl)-carbamic acid, benzyl ester (3) inhibits (alpha-CT, a prototypical serine protease, in the presence of Zn(II) ion. They constitute a novel class of small molecule inhibitors for alpha-CT believed to inhibit the enzyme by forming a ternary complex consisting of alpha-CT, Zn(II) ion, and the inhibitor. (C) 2003 Elsevier Ltd. All rights reserved.
• Potent and systemically active aminopeptidase N inhibitors designed from active-site investigation
  作者：Marie Claude Fournie-Zaluski、Pascale Coric、Serge Turcaud、Luce Bruetschy、Evelyne Lucas、Florence Noble、Bernard P. Roques

  DOI：10.1021/jm00085a013

  日期：1992.4

  Derivatives of amino acids bearing various zinc-coordinating moieties (SH, COOH, CONHOH, and PO3H2) were synthesized and tested for their ability to inhibit aminopeptidase N (APN). Among them, beta-amino thiols were found to be the most efficient with IC50's in the 11-50 nM range. These results suggest that the S1 subsite of APN is a deep but not very large hydrophobic pocket, optimally fitting side chains of moderate bulk endowed with some degree of freedom. The iv administration of the inhibitors, alone, did not induce antinociceptive responses on the hot plate test in mice. However, in presence of 10 mg/kg acetorphan, a prodrug of the neutral endopeptidase inhibitor thiorphan, these compounds gave a large increase in the jump latency time with ED50's of 2 and 2.4 mg/kg for the disulfides of methioninethiol [H2NCH(CH2CH2SCH3)CH2S]2 and S-oxomethioninethiol [H2NCH(CH2CH2S(O)CH3)CH2S]2, respectively. These results show that the disulfide forms of beta-amino thiols are efficient prodrugs of aminopeptidase N inhibitors capable of crossing the blood-brain barrier.