(S)-N-Boc-3,3-二甲基吡咯烷-2-甲酸 | 174060-98-1

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - BOC-氨基酸
• 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: (S)-N-Boc-3,3-二甲基吡咯烷-2-甲酸
• 中文别名: (S)-N-叔丁氧羰基-3,3-二甲基吡咯烷-2-甲酸
• 英文名称: 1-(tert-butoxycarbonyl)-3,3-dimethyl-D,L-proline
• 英文别名: (2S)-3,3-dimethyl-N-tertbutoxycarbonylproline；t-butyloxy-carbonyl-3,3-dimethyl-dl-proline；t-butyloxycarbonyl-3,3-dimethyl-dl-proline；(2S)-3,3-Dimethyl-N-(Boc) proline；Boc-(2S)-3,3-dimethyl-2-pyrrolidenecarboxylic Acid；(2S)-3,3-dimethyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
• CAS: 174060-98-1
• 化学式: C₁₂H₂₁NO₄
• 分子量: 243.303
• InChiKey: FVTWJYOGVFLUNJ-MRVPVSSYSA-N

物化性质

• 熔点：
  124-127°C
• 密度：
  1.117
• 溶解度：
  可溶于氯仿、二甲基亚砜、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090
• 储存条件：
  -20°C 冰箱

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(S)-3,3-Dimethyl-2-methylcarbamoyl-pyrrolidine-1-carboxylic acid tert-butyl ester	213882-58-7	C13H24N2O3	256.345

反应信息

• 作为反应物：
  描述：

  (S)-N-Boc-3,3-二甲基吡咯烷-2-甲酸 在 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 26.0h， 生成 (S)-1-Acetyl-3,3-dimethyl-pyrrolidine-2-carboxylic acid methylamide
  参考文献：
  名称：

  Alkyl 3-Position Substituents Retard the Isomerization of Prolyl and Hydroxyprolyl Amides in Water

  摘要：

  The influence of alkyl 3-position substituents on the rate of amide isomerization N-terminal to proline and hydroxyproline has been explored via the synthesis and analysis of (2S)-N-(acetyl)proline N'-methylamide (1), (2S,4R)- and (2S,4S)-N-acetyl-4-hydroxyproline N'-methylamides 2 and 3, and their respective 3,3-dimethyl analogues 4-6. The relative populations of the amide cis and trans isomers as well as the rates for cis-to-trans and trans-to-cis isomerization of 1-6 in water were ascertained by NMR spectroscopy and magnetization transfer experiments. The relative populations of free C-terminal and hydrogen-bonded amides in the gamma-turn conformation were also estimated by integrating the N-H stretch absorbances in the FT-IR spectra of 1 and 4 in CHCl3. In addition, the structure of the amide trans isomer of (2S,4S)-N-acetyl-3,3-dimethyl-4-hydroxyproline N'-methylamide (6) was determined in the solid state by X-ray crystallographic analysis. In prolyl peptides 1-6, the 3,3-dimethyl and hydroxyl substituents had little effect on the amide isomer equilibrium. A dramatic decrease in the rate of cis-to-trans amide isomerization was observed for N-acetyl-3,3-dimethylproline N'-methylamide (4), which exhibited a k(ct) nearly 7-fold slower than that of 1. Similar effects of the 3,3-dimethyl substituents were observed, albeit to a lesser degree, in the cases of the hydroxyprolyl peptides. The FT-IR data for 4 and X-ray data for 6 both demonstrated that the 3,3-dimethyl substituents restricted the proline psi dihedral angle and prevented the formation of a gamma-turn conformation, having a seven-membered hydrogen bond between the C-terminal amide NH and N-terminal amide carbonyl. Furthermore, restriction of the psi dihedral angle by the methyl groups was observed in systematic computational conformational analyses of 1-6, in which the psi and omega dihedral angles were rotated at 30 degrees intervals and the energies of the local minima were determined. Retardation of the rate of cis-to-trans amide isomerization in the dimethyl analogues may be attributed to steric interactions favoring a psi dihedral angle at which the C-terminal amide carbonyl destabilizes the transition state through Coulomb repulsion of either the developing nitrogen lone pair or the carbonyl oxygen of the pyramidalized N-terminal amide. The consequences of S-alkyl and 4-hydroxyl substituents on the rate of proline amide isomerization in water, which was observed to decrease in the order 1 approximate to 3 > 2 > 6 > 5 > 4, may result from influences on the psi, dihedral angle geometry, inductive effects, and intramolecular hydrogen bonding.

  DOI：

  10.1021/jo980673o
• 作为产物：
  描述：

  (2S,4S)-3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl ester 在 palladium dihydroxide 偶氮二异丁腈 、 氢气 、 三正丁基氢锡 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 4.0 ℃ 、506.62 kPa 条件下， 反应 26.5h， 生成 (S)-N-Boc-3,3-二甲基吡咯烷-2-甲酸
  参考文献：
  名称：

  Regioselective Enolization and Alkylation of 4-Oxo-N-(9-phenylfluoren-9-yl)proline:  Synthesis of Enantiopure Proline−Valine and Hydroxyproline−Valine Chimeras

  摘要：

  The regioselective enolization of 4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (5) followed by alkylation with different alkyl halides has been used to synthesize a variety of beta-alkylproline derivatives. In particular, enolization of 5 with 400 mol % of KN(SiMe(3))(2) and alkylation with iodomethane provided 3,3-dimethyl-4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (7a) in excellent yield. Subsequent hydride reduction of ketone 7a and protecting group exchange by hydrogenation in the presence of di-tert-butyl dicarbonate provided enantiopure (2S,4R)- and (2S,4S)-3,3-dimethyl-4-hydroxy-N-(BOC)prolines. 2. Hydroxyproline-valine chimeras (2S,4R)- and (2S,4S)-2 are each synthesized from hydroxyproline in six steps and 27% respective overall yield. Deoxygenation of 3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl esters 9 via their conversion to xanthates 10 followed by tributylstannane-mediated reduction provided 3,3-dimethyl-N-(9-phenylfluoren-9-yl)proline benzyl ester (11) in excellent yield. Hydrogenation of 11 with Pearlman's catalyst in the presence of di-tert-butyl dicarbonate then furnished (2S)-3,3-dimethyl-N-(BOC)proline (1) in the last step of an eight-step synthesis (41% overall yield) from hydroxyproline. Both proline-valine and hydroxyproline-valine chimeras 1 and 2 were designed to serve as tools for studying the conformational requirements of biologically active peptides.

  DOI：

  10.1021/jo9514984
• 作为试剂：
  描述：

  (S)-N-Boc-3,3-二甲基吡咯烷-2-甲酸 、 碳酸叔丁基-2,4,5-三氯苯酯 在 (S)-N-Boc-3,3-二甲基吡咯烷-2-甲酸 作用下， 生成
  参考文献：
  名称：

  Journal of labelled compounds and radiopharmaceuticals 1996, 38, 483-488

  摘要：

  DOI：

文献信息

• Thrombin inhibitors
  申请人：——

  公开号：US20020119992A1

  公开（公告）日：2002-08-29

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1 or a pharmaceutically acceptable salt thereof, e.g. where R 3 is —CH 2 NH 2 , —CH 2 CH 2 NH 2 , or —CH 2 NHC(O)OC(CH 3 ) 3 .

  该发明的化合物在抑制凝血酶和相关血栓闭塞方面具有以下结构： 1 或其药用可接受的盐，例如其中R 3 为—CH 2 NH 2 ，—CH 2 CH 2 NH 2 ，或—CH 2 NHC(O)OC(CH 3 ) 3 。
• Hepatitis C Virus Inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US20150023913A1

  公开（公告）日：2015-01-22

  The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.

  本公开涉及抗病毒化合物，更具体地涉及能够抑制由丙型肝炎病毒（HCV）编码的NS5A蛋白功能的化合物组合，包括这种组合的组成物，以及抑制NS5A蛋白功能的方法。
• Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method
  申请人：——

  公开号：US20020019411A1

  公开（公告）日：2002-02-14

  Dipeptidyl peptidase IV (DP 4) inhibiting compounds are provided having the formula 1 where x is 0 or 1 and y is 0 or 1 (provided that x=1 when y=0 and x=0 when y=1); n is 0 or 1; X is H or CN; and wherein R 1 , R 2 , R 3 and R 4 are as described herein. A method is also provided for treating diabetes and related diseases, especially Type II diabetes, and other diseases as set out herein, employing such DP 4 inhibitor or a combination of such DP 4 inhibitor and one or more of another antidiabetic agent such as metformin, glyburide, troglitazone, pioglitazone, rosiglitazone and/or insulin and/or one or more of a hypolipidemic agent and/or anti-obesity agent and/or other therapeutic agent.

  提供了具有公式1的抑制二肽基肽酶IV（DP 4）的化合物，其中x为0或1，y为0或1（前提是当y=0时，x=1，当y=1时，x=0）；n为0或1；X为H或CN；其中R1、R2、R3和R4如本文所述。还提供了一种治疗糖尿病和相关疾病，特别是II型糖尿病以及本文中列出的其他疾病的方法，使用这种DP 4抑制剂或这种DP 4抑制剂与另一种或多种抗糖尿病药物（如二甲双胍、格列本脲、曲格列酮、吡格列酮、罗格列酮和/或胰岛素）的组合，以及一种或多种降脂药物和/或抗肥胖药物和/或其他治疗药物。
• Histidine derivatives
  申请人：Reckitt & Colman Products Limited

  公开号：US04060603A1

  公开（公告）日：1977-11-29

  Compounds of the formula ##STR1## wherein R, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 represent certain specified substituent groups. The compounds exhibit activity in the reserpine induced hypothermia test.

  化合物的公式为##STR1## 其中R，R.sup.1，R.sup.2，R.sup.3和R.sup.4代表特定的取代基团。这些化合物在利血平诱导的体温降低试验中表现出活性。
• Combinations of Hepatitis C Virus Inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20160158200A1

  公开（公告）日：2016-06-09

  The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.

  本公开涉及抗病毒化合物，更具体地涉及能够抑制丙型肝炎病毒（HCV）编码的NS5A蛋白功能的化合物组合，包含这种组合的组合物，以及抑制NS5A蛋白功能的方法。