(S)-2-amino-3-phenyl-N-[(R)-1-phenylethyl]propanamide | 133287-30-6

• 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: (S)-2-amino-3-phenyl-N-[(R)-1-phenylethyl]propanamide
• 英文别名: (2S)-2-amino-3-phenyl-N-[(1R)-1-phenylethyl]propanamide
• CAS: 133287-30-6
• 化学式: C₁₇H₂₀N₂O
• 分子量: 268.359
• InChiKey: VFMMDUZLZCLHHO-CJNGLKHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-3-phenyl-N-[(R)-1-phenylethyl]propanamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成
  参考文献：
  名称：

  Chymotrypsin inhibitory conformation induced by amino acid side chain–side chain intramolecular CH/π interaction

  摘要：

  Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/pi interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2](n)-C6H5 (n = 0-4) have been assayed for chymotrypsin, They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (K-1 3.6 x 10(-6) M), The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition, The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically, The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active, When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (K-1 = 6.1 x 10(-7) M; this dipeptide is one of the most potent chymotrypsin inhibitors to date), H-1 NMR conformational analyses of these dipeptide amide derivatives show the CH/pi: interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition, These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S-1 site, while the hydrophobic core constructed by D-Leu-Phe CH/pi interaction fits the chymotrypsin S-2 or S-1' site.

  DOI：

  10.1039/p19960002479
• 作为产物：
  描述：

  (S)-2-[N-Boc-amino]-3-phenyl-N-[(R)-1-phenylethyl]propanamide 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以97%的产率得到(S)-2-amino-3-phenyl-N-[(R)-1-phenylethyl]propanamide
  参考文献：
  名称：

  氨基酸衍生手性胺通过光学拆分合成光学活性γ-戊内酯和γ-壬内酯

  摘要：

  光学活性的 γ-戊内酯和 γ-壬内酯已使用新开发的 L-苯丙氨酸衍生的手性胺通过光学拆分合成。通过用旋光拆分剂酰胺化，两种外消旋的 γ-内酯都转化为相应的非对映体酰胺。非对映体酰胺的分级结晶、每个非对映体的重结晶和随后的水解得到具有足够对映体过量和分离产率的光学活性γ-戊内酯和γ-壬内酯。水解后回收旋光拆分剂。

  DOI：

  10.3987/com-09-11863

文献信息

• Asymmetric Hydrogenation Catalyzed by the (Achiral Base)bis(dimethylglyoximato)cobalt(II)–Chiral Cocatalyst System. The Preparation of a New Type of Chiral Cocatalyst and Its Application to the Asymmetric Hydrogenation of Methyl<i>N</i>-(Acetylamino)acrylate and Benzil
  作者：Seiji Takeuchi、Yoshiaki Ohgo

  DOI：10.1246/bcsj.54.2136

  日期：1981.7

  As a new type of chiral cocatalyst in the achiral base-coordinated bis(dimethylglyoximato)cobalt(II)–chiral cocatalyst system, tertiary amines with an amide group at α- or β-carbon were prepared, and asymmetric hydrogenation was examined by using them. The optical yield reached 34.5% enantiomeric excess(ee) by using N-[(2S,3S)-2-acetoxy-3-dimetnylamino-3-phenylpropionyl]-(R)-α-methylbenzylamine; this is the highest value attained so far in the asymmetric hydrogenation of methyl N-(acetylamino)acrylate with this system. The enantioselectivity in the hydrogenation of methyl N-(acetylamino)acrylate was reversed with a configurational alteration of the α-methylbenzylamine moiety of N-[N,N-dimethyl-(S)-phenylalanyl]-α-methylbenzylamine, while it was not reversed in the hydrogenation of benzil by the configurational alteration. From these facts, it is deduced that the hydrogen bond between amide groups of the chiral amino carboxamides and methyl N-(acetylamino)acrylate may act as an attractive force to enhance the enantioselectivity of the asymmetric hydrogenation.

  在非手性基团配位的双(二甲基乙二肟)钴(II)–手性共催化剂体系中，作为一种新型的手性共催化剂，制备了在α-或β-碳上含有酰胺基的三级胺，并使用它们进行了不对称氢化反应的研究。通过使用N-[(2S,3S)-2-乙酰氧基-3-二甲基氨基-3-苯基丙酰基]-(R)-α-甲基苯乙胺，光学产率达到了34.5%的ee值；这是迄今为止在该体系下对甲基N-(乙酰氨基)丙烯酸酯进行不对称氢化反应中获得的最高值。当N-[N,N-二甲基-(S)-苯丙氨酰]-α-甲基苯乙胺的α-甲基苯乙胺部分发生构型改变时，甲基N-(乙酰氨基)丙烯酸酯的氢化反应中的立体选择性发生了反转，而通过构型改变对苯偶酰的氢化反应中的立体选择性没有发生反转。从这些事实可以推断，手性氨基酸酰胺与甲基N-(乙酰氨基)丙烯酸酯之间的酰胺基氢键可能作为一种吸引力，增强不对称氢化反应的立体选择性。
• Stereochemical effects in mass spectrometry. 7. Determination of absolute configuration of some organic molecules by reaction mass spectrometry
  作者：Yao-Zu Chen、Hung Li、Hou-Jun Yang、Su-Ming Hua、Hai-Quan Li、Fan-Zhi Zhao、Nen-Yu Chen

  DOI：10.1002/oms.1210231205

  日期：1988.12

  AbstractIt was found that in the chemical ionization (isobutane) mass spectra of some asymmetric secondary alcohols and α‐amino acids, when a pair of enantiomers (such as R‐ and S‐2‐phenyIbutyric anhydride, R‐ and S‐mandelic acid, R‐ and S‐2‐methylbutanoic acid or R‐ and S‐α‐phenyl ethyl amine) were used as reaction reagents, the relative abundances of characteristic ions formed by the stereoselective reaction between sample and reagent of the same configuration were much higher than those ions formed by the sample and a reagent of a different configuration. The absolute configuration of the sample molecule may be predicted by examination of mass spectra of the sample measured with R‐ and S‐reagent respectively. This approach proved to be a convenient way for determination of the absolute configurations of organic molecules on a micromole level by mass Spectrometry.
• Synthesis of Optically Active γ-Valerolactone and γ-Nonanolactone via Optical Resolution Using Chiral Amine Derived from Amino Acid
  作者：Hiroaki Toshima、Kenichi Yumoto、Morifumi Hasegawa

  DOI：10.3987/com-09-11863

  日期：——

  Optically active γ-valerolactone and γ-nonanolactone have been synthesized via optical resolution using a newly developed chiral amine derived from L-phenylalanine. Both racemic γ-lactones were transformed to corresponding diastereomeric amides by amidation with the optical resolution agent. Fractional crystallization of diastereomeric amides, recrystallization of each diastereomer, and subsequent

  光学活性的 γ-戊内酯和 γ-壬内酯已使用新开发的 L-苯丙氨酸衍生的手性胺通过光学拆分合成。通过用旋光拆分剂酰胺化，两种外消旋的 γ-内酯都转化为相应的非对映体酰胺。非对映体酰胺的分级结晶、每个非对映体的重结晶和随后的水解得到具有足够对映体过量和分离产率的光学活性γ-戊内酯和γ-壬内酯。水解后回收旋光拆分剂。
• Chymotrypsin inhibitory conformation induced by amino acid side chain–side chain intramolecular CH/π interaction
  作者：Yasuyuki Shimohigashi、Iori Maeda、Takeru Nose、Koichi Ikesue、Hiroshi Sakamoto、Tomohisa Ogawa、Yuzuru Ide、Megumi Kawahara、Takashi Nezu、Yoshihiro Terada、Keiichi Kawano、Motonori Ohno

  DOI：10.1039/p19960002479

  日期：——

  Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/pi interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2](n)-C6H5 (n = 0-4) have been assayed for chymotrypsin, They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (K-1 3.6 x 10(-6) M), The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition, The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically, The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active, When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (K-1 = 6.1 x 10(-7) M; this dipeptide is one of the most potent chymotrypsin inhibitors to date), H-1 NMR conformational analyses of these dipeptide amide derivatives show the CH/pi: interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition, These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S-1 site, while the hydrophobic core constructed by D-Leu-Phe CH/pi interaction fits the chymotrypsin S-2 or S-1' site.