5(R)-5-<1(S)-1-(N-Boc-amino)-3-methylbutyl>dihydrofuran-2(3H)-one | 105018-83-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 5(R)-5-<1(S)-1-(N-Boc-amino)-3-methylbutyl>dihydrofuran-2(3H)-one
• 英文别名: (5R)-5-[(1'S)-1-(N-Boc-amino)-3-methylbutyl]dihydrofuran-2(3H)-one；(5R,1'S)-5-[1'[(tert-butoxycarbonyl)amino]-3'-methylbutyl]-dihydrofuran-2(3H)-one；(5S,1'R)-5-[1'-[(tert-butoxycarbonyl)amino]-3'-methylbutyl]dihydrofuran-2(3H)-one；tert-butyl (1S)-3-methyl-1-[(2R)-5-oxotetrahydro-2-furanyl]butylcarbamate；tert-butyl N-[(1S)-3-methyl-1-[(2R)-5-oxooxolan-2-yl]butyl]carbamate
• CAS: 105018-83-5
• 化学式: C₁₄H₂₅NO₄
• 分子量: 271.357
• InChiKey: VBSGVYVHEPQKTH-WDEREUQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5(R)-5-<1(S)-1-(N-Boc-amino)-3-methylbutyl>dihydrofuran-2(3H)-one 、 碘甲烷 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以71%的产率得到tert-butyl (1S)-3-methyl-1-[(2R,4R)-4-methyl-5-oxotetrahydro-2-furanyl]butylcarbamate
  参考文献：
  名称：

  [EN] NOVEL SULFONE AMIDE DERIVATIVES CAPABLE OF INHIBITING BACE
  [FR] NOUVEAUX DERIVES SULFONAMIDE CAPABLES D'INHIBER BACE

  摘要：

  本发明涉及本公开中定义的式1的磺酰脒衍生物，该衍生物抑制BACE（或β-分泌酶）的活性。这些磺酰脒衍生物可用于治疗和预防由β-淀粉样蛋白产生引起的阿尔茨海默病及相关疾病，通过抑制BACE的活性。

  公开号：

  WO2005030709A1
• 作为产物：
  描述：

  (4RS,5S)-N-Boc-5-amino-4-hydroxy-7-methyloct-2-ynoic acid ethyl ester 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以 乙酸乙酯 、 甲苯 为溶剂， 反应 5.5h， 生成 5(R)-5-<1(S)-1-(N-Boc-amino)-3-methylbutyl>dihydrofuran-2(3H)-one
  参考文献：
  名称：

  含羟基乙烯二肽等排体的β-分泌酶抑制剂的合成

  摘要：

  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。

  DOI：

  10.1080/00397910600977509

文献信息

• Direct Catalytic Asymmetric Mannich-Type Reactions of γ-Butenolides: Effectiveness of Brønsted Acid in Chiral Metal Catalysis
  作者：Akitake Yamaguchi、Shigeki Matsunaga、Masakatsu Shibasaki

  DOI：10.1021/ol800756r

  日期：2008.6.5

  Direct catalytic asymmetric Mannich-type reactions of gamma-butenolides are described. A chiral Lewis acid/amine base/Bronsted acid combination was used to catalyze a gamma-addition of gamma-butenolides to N-diphenylphosphinoyl imines, affording the products in up to >99% yield, anti/syn = >97:3, and 84% ee. The use of a catalytic amount of TfOH in addition to La(OTf)3/Me-PyBox/TMEDA was important

  描述了γ-丁烯内酯的直接催化不对称曼尼希型反应。手性路易斯酸/胺碱/布朗斯台德酸的组合用于催化γ-丁烯内酯向N-二苯基膦酰基亚胺的γ加成反应，从而使产物收率最高> 99％，反/ syn => 97：3，并且84％ee。除La（OTf）3 / Me-PyBox / TMEDA外，还使用催化量的TfOH对于提高收率和立体选择性很重要。
• [EN] BICYCLIC COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF<br/>[FR] COMPOSES BICYCLIQUES INHIBANT L'ACTIVITE DE LA BETA-SECRETASE ET PROCEDES D'UTILISATION ASSOCIES
  申请人：ZAPAQ INC

  公开号：WO2006034277A1

  公开（公告）日：2006-03-30

  The present invention provides bicyclic beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer’s disease.

  本发明提供了双环β-分泌酶抑制剂及其用途，包括用于治疗阿尔茨海默病的方法。
• Synthesis and preliminary evaluation of peptidomimetic inhibitors of human β-secretase
  作者：Yan Niu、Yuehua Wang、Xiaomin Zou、Xiaoming Yang、Chao Ma、Yang Lü、Bo Zhou、Yue Yuan、Guanhua Du、Ping Xu

  DOI：10.1016/j.ejmech.2010.01.044

  日期：2010.5

  Based on the structure of OM99-2 and the X-ray crystal structure of its complex with beta-secretase, a series of compounds containing the Leu*Ala hydroxyethylene isostere as a scissile bond substitution were designed. 31 compounds were synthesized and their beta-secretase inhibition activities were measured. It was found that isobutyl group was a better R(3) substitution as C-terminus in our target compounds, and 4-nitrobenzyl group was the best R(2) side chain. With the aid of molecular modeling, the binding modes of compounds 9 and 22 with beta-secretase were compared. The result revealed a stronger bonding mode of 22 than 9. This explored that the optimal length of this series of peptidomimetic inhibitors was P3-P2'. The molecular weights of compounds with this length are around 600. (C) 2010 Elsevier Masson SAS. All rights reserved.
• A short, stereoselective synthesis of the lactone precursor to 2R,4S,5S hydroxyethylene dipeptide isosteres
  作者：Andrew H. Fray、Robert L. Kaye、Edward F. Kleinman

  DOI：10.1021/jo00375a014

  日期：1986.12
• Design of Potent Inhibitors for Human Brain Memapsin 2 (β-Secretase)
  作者：Arun K. Ghosh、Dongwoo Shin、Debbie Downs,、Gerald Koelsch、Xinli Lin、Jacques Ermolieff、Jordan Tang

  DOI：10.1021/ja000300g

  日期：2000.4.1