A series of novel homochiral β-oligopeptides bearing aryl side chains was designed and synthesized from （S）-β-phenyl-β-amino acid derivatives by solution-phase methods. By means of circular dichroism（CD）, Fouri...A series of novel homochiral β-oligopeptides bearing aryl side chains was designed and synthesized from （S）-β-phenyl-β-amino acid derivatives by solution-phase methods. By means of circular dichroism（CD）, Fourier- transform infrared spectrometry（FTIR）, powder X-ray diffraction analysis（XRD） and density functional theory（DFT） calculations, we suggest that dipeptide P-2 and tripeptide P-3 adopt random coil-like conformations, pentapeptide P-5 and hexapeptide P-6 adopt stable 12-helix conformations in both solution and solid-state. Meanwhile, tetrapeptide P-4 adopt random coil-like conformation in solution and adopt 12-helix conformation in solid state.展开更多
A novel organophosphorus compound containing the structure of bothβ-amino acid andβ-aminophosphonate is designed and synthesized.Arbuzov reaction with P（OEt）_3,the N-Boc protected iodide 3 cannot provide the desir...A novel organophosphorus compound containing the structure of bothβ-amino acid andβ-aminophosphonate is designed and synthesized.Arbuzov reaction with P（OEt）_3,the N-Boc protected iodide 3 cannot provide the desired product but 2-oxazolidinone 4 because of the neighboring-group participation of the Boc moiety.To avoid the intramolecular participation of the carbamates,the Ts protecting group is employed and the Ts-protected iodide 5 affords the target product successfully.展开更多
Sitagliptin is the first new anti-diabetic drug in DPP-Ⅳ inhibitor class. The general synthesis of sitagliptin is by coupling of the β-amino acid fragment with the heterocycle fragment. Though the specific β-amino ...Sitagliptin is the first new anti-diabetic drug in DPP-Ⅳ inhibitor class. The general synthesis of sitagliptin is by coupling of the β-amino acid fragment with the heterocycle fragment. Though the specific β-amino acid can be easily made from the corresponding R-amino acid by Arndt-Eistert hornologation, the optically pure precursor R-amino acid is difficult to prepare. We herein reported a practical protocol to make the trifluorophenyl substituted R-amino acid 4 in 〉99.9% ee and 40.3% yield by the enzymatic resolution employing enantioselective hydrolysis and a general separation procedure. This protocol requires only cheap starting materials and friendly reaction condition. The procedure not only allows people to prepare the drug substance, but also provides an alternative method for prepareing the rare α-amino acid and the subsequent β-amino acid.展开更多
Halogen substituted β-amino acids, D,L-3-amino-3-（4-fluoro）phenylpropionic acid（D,L-HL1, 1） and D,L-3-amino-3-（4-bromo）phenylpropionic acid（D,L-HL2, 2）, as well as their Cu（II） coordination complexes [Cu（L...Halogen substituted β-amino acids, D,L-3-amino-3-（4-fluoro）phenylpropionic acid（D,L-HL1, 1） and D,L-3-amino-3-（4-bromo）phenylpropionic acid（D,L-HL2, 2）, as well as their Cu（II） coordination complexes [Cu（L1）2（CH3OH）2].2CH3OH（3） and [Cu（L2）2（CH3OH）2]-2CHaOH（4） were investigated and their single crystal structures were discussed in details. Supramolecular helical chains were found in β-amino acids 1 and 2 while there was no helix in their coordination complexes 3 and 4. The formation of supramolecular helixes could be due to the hydrogen bonds between terminal -NH3＋ and adjacent -COO- in β-amino acids 1 and 2. While, this kind of hydrogen bonds could not be observed in their Cu（II） coordination complexes 3 and 4, in which central-symmetrical dimers could be formed via coplanar coordinated bonds（N-Cu-O） between -NH2 and -COO-.展开更多
基金the National Natural Science Foundation of China（No.21172217）.
文摘A series of novel homochiral β-oligopeptides bearing aryl side chains was designed and synthesized from （S）-β-phenyl-β-amino acid derivatives by solution-phase methods. By means of circular dichroism（CD）, Fourier- transform infrared spectrometry（FTIR）, powder X-ray diffraction analysis（XRD） and density functional theory（DFT） calculations, we suggest that dipeptide P-2 and tripeptide P-3 adopt random coil-like conformations, pentapeptide P-5 and hexapeptide P-6 adopt stable 12-helix conformations in both solution and solid-state. Meanwhile, tetrapeptide P-4 adopt random coil-like conformation in solution and adopt 12-helix conformation in solid state.
文摘A novel organophosphorus compound containing the structure of bothβ-amino acid andβ-aminophosphonate is designed and synthesized.Arbuzov reaction with P（OEt）_3,the N-Boc protected iodide 3 cannot provide the desired product but 2-oxazolidinone 4 because of the neighboring-group participation of the Boc moiety.To avoid the intramolecular participation of the carbamates,the Ts protecting group is employed and the Ts-protected iodide 5 affords the target product successfully.
基金supported in part by grant from Science and Technology Program of Guangdong Province(No. 2007B031503005).
文摘Sitagliptin is the first new anti-diabetic drug in DPP-Ⅳ inhibitor class. The general synthesis of sitagliptin is by coupling of the β-amino acid fragment with the heterocycle fragment. Though the specific β-amino acid can be easily made from the corresponding R-amino acid by Arndt-Eistert hornologation, the optically pure precursor R-amino acid is difficult to prepare. We herein reported a practical protocol to make the trifluorophenyl substituted R-amino acid 4 in 〉99.9% ee and 40.3% yield by the enzymatic resolution employing enantioselective hydrolysis and a general separation procedure. This protocol requires only cheap starting materials and friendly reaction condition. The procedure not only allows people to prepare the drug substance, but also provides an alternative method for prepareing the rare α-amino acid and the subsequent β-amino acid.
基金Supported by the National Natural Science Foundation of China（Nos.21071018, 21271026）.
文摘Halogen substituted β-amino acids, D,L-3-amino-3-（4-fluoro）phenylpropionic acid（D,L-HL1, 1） and D,L-3-amino-3-（4-bromo）phenylpropionic acid（D,L-HL2, 2）, as well as their Cu（II） coordination complexes [Cu（L1）2（CH3OH）2].2CH3OH（3） and [Cu（L2）2（CH3OH）2]-2CHaOH（4） were investigated and their single crystal structures were discussed in details. Supramolecular helical chains were found in β-amino acids 1 and 2 while there was no helix in their coordination complexes 3 and 4. The formation of supramolecular helixes could be due to the hydrogen bonds between terminal -NH3＋ and adjacent -COO- in β-amino acids 1 and 2. While, this kind of hydrogen bonds could not be observed in their Cu（II） coordination complexes 3 and 4, in which central-symmetrical dimers could be formed via coplanar coordinated bonds（N-Cu-O） between -NH2 and -COO-.
