N-[(S)-2-Hydroxy-3-phenylpropanoyl]pyrrolidine | 121378-64-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: N-[(S)-2-Hydroxy-3-phenylpropanoyl]pyrrolidine
• 英文别名: (2S)-2-hydroxy-3-phenyl-1-pyrrolidin-1-ylpropan-1-one
• CAS: 121378-64-1
• 化学式: C₁₃H₁₇NO₂
• 分子量: 219.283
• InChiKey: IRHYIYVSUUDRRL-LBPRGKRZSA-N

物化性质

• 熔点：
  98-99 °C
• 沸点：
  408.0±38.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-[(S)-2-Hydroxy-3-phenylpropanoyl]pyrrolidine 在 甲基三辛基氯化铵 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 (S)-3-benzyloxy-4-phenyl-2-butanone
  参考文献：
  名称：

  立体选择性钛介导的α-苄氧基甲基酮的醛醇缩合反应

  摘要：

  在手性α-苄氧基甲基酮与多种醛的TiCl 3（i- PrO）介导的羟醛反应中获得了良好水平的1,4-抗不对称诱导。这种方法学代表了一种新的方法，可进行底物控制的乙酸羟醛醛缩反应，该方法能够以直接的方式提供高度官能化的片段，这可能对设计更有效的合成方法有用。

  DOI：

  10.1016/j.tet.2012.09.096
• 作为产物：
  描述：

  四氢吡咯 、 L-(-)-3-苯基乳酸 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 N-[(S)-2-Hydroxy-3-phenylpropanoyl]pyrrolidine
  参考文献：
  名称：

  Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement

  摘要：

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.

  DOI：

  10.1021/jm00088a006

文献信息

• Simple and Efficient Preparation of Enantiopure Alkyl α-Hydroxyalkyl Ketones
  作者：Mònica Ferreró、Marta Galobardes、Ricardo Martín、Tomàs Montes、Pedro Romea、Roser Rovira、Fèlix Urpí、Jaume Vilarrasa

  DOI：10.1055/s-2000-7611

  日期：——

  The acylation reaction of organolithium reagents with pyrrolidine-derived α-benzyloxy and α-silyloxy carboxamides provides a simple and high-yielding method for the preparation of enantiopure α-benzyloxy and α-silyloxy ketones.

  有机锂试剂与吡咯烷衍生的δ-苄氧基和δ-硅氧基羧酰胺的酰化反应为制备不纯的δ-苄氧基和δ-硅氧基酮提供了一种简单而高产的方法。
• Non-peptide renin inhibitors
  申请人：ABBOTT LABORATORIES

  公开号：EP0364804A1

  公开（公告）日：1990-04-25

  A renin inhibiting compound of the formula: wherein A is a substituent; R1 is hydrogen, loweralkyl, substituted loweralkyl or loweralkenyl; X is CH2, CHOH, C(O), O, S, S(O), S02, NH, N(O) or -P(O)O-; R3 is loweralkyl, loweralkenyl or substituted loweralkyl; and T is mimic of the Leu-Val cleavage site of angiotensinogen; or a pharmaceutically acceptable salt, ester or prodrug thereof.

  式中的肾素抑制化合物： 其中 A 是取代基；R1 是氢、低级烷基、取代的低级烷基或低级烯基；X 是 CH2、CHOH、C(O)、O、S、S(O)、S02、NH、N(O)或-P(O)O-；R3 是低级烷基、低级烯基或取代的低级烷基；T 是血管紧张素原的 Leu-Val 裂解位点的模拟物；或其药学上可接受的盐、酯或原药。
• A simple procedure for the preparation of enantiopure ethyl α-hydroxyalkyl ketones
  作者：Ricardo Martín、Oscar Pascual、Pedro Romea、Roser Rovira、Fèlix Urpí、Jaume Vilarrasa

  DOI：10.1016/s0040-4039(97)00107-x

  日期：1997.3

  Amides derived from pyrrolidine and methyl (S)-lactate, methyl (S)-2-hydroxy-3-phenylpropanoate, or methyl (S)-2-hydroxy-3-methylbutanoate, after O-benzylation and O-silylation have been treated with EtLi or EtMgCl under suitable conditions, to give excellent overall yields of enantiopure ethyl ketones. The chelating ability of alpha-OBn amides (and even of alpha-O-TBS amides, which has been demonstrated by NMR to be better than that of N-OMe amides) accounts for the performance of the approach. (C) 1997 Elsevier Science Ltd.
• WANNER, KLAUS TH.;HOFNER, GEORGE, ARCH. PHARM., 322,(1989) N, C. 93-97
  作者：WANNER, KLAUS TH.、HOFNER, GEORGE

  DOI：——

  日期：——
• Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement
  作者：William R. Baker、Anthony K. L. Fung、Hollis D. Kleinert、Herman H. Stein、Jacob J. Plattner、Yoek Lin Armiger、Stephen L. Condon、Jerome Cohen、David A. Egan

  DOI：10.1021/jm00088a006

  日期：1992.5

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.