Polymers
·
2018
·Vol. 10
·期 9
·936
·
IF 2.935
Chonglong Li,Xunhui Xu,Lei Xu,Na Liu
An optically active, amphiphilicmeta-phenylene ethynylene (m-PE) bearing a chiral amide pendant was designed and synthesized. Living polymerization ofm-PE using alkyne-Pd(II) as the initiator afforded well-defined poly(meta-phenylene ethynylene) (m-PPE). Thesem-PPEs were found to have a stable helical conformation in THF, 1,4-dioxane, and CH3CN and showed split Cotton effects over the range of 245–400 nm. The positive first Cotton effect was observed at a wavelength of approximately 308 nm, and the negative second Cotton effect was observed at a wavelength of approximately 289 nm. Them-PPEs exhibited helical conformational changes in different mixed solvents and showed effective solvent-dependent helix inversion in CHCl3/THF solutions. The sign of the Cotton effect ofm-PPE was inverted at 25 °C by varying the mixing ratio of THF and CHCl3. Finally, amphiphilic poly(meta-phenylene ethynylene)-block-polyisocyanide containing hydrophilic PPE and hydrophobic PPI segments were facilely prepared using Pd(II)-terminatedm-PPE as the macroinitiator. This block copolymer can self-assemble into well-defined spherical nanostructures in a selective THF/CH3OH solution. This efficient polymerization will open up enormous opportunities for the preparation of functional amphiphilic block copolymers in a wide variety of fields.
研究领域:
高分子化学
·
材料科学
✓ 已验证
DOI
高影响因子
MACROMOLECULES
·
2014
·
IF 5.927
Yuan-Yuan Zhu,Ting-Ting Yin,Xue-Liang Li,Ming Su,Ya-Xin Xue,Zhi-Peng Yu,Na Liu,Jun Yin,Zong-Quan Wu
Two allene derivatives, l- and d-N-(1-(octylamino)-1-oxopropan-2-yl)-4-(propa-1,2-dien-1-yloxy)benzamide (l-1 and d-1), bearing chiral amide pendants were designed and synthesized. Living polymerizations of l-1 and d-1 with allylnickel complex as a catalyst afforded poly-l-1m and poly-d-1m with controlled molecular weights and narrow molecular weight distributions. These polymers were found to possess a stable helical conformation with a preferred handedness in aprotic solvents on the basis of their circular dichroism (CD) spectra and specific rotation as well as computer simulation. The helical conformation of the polymers was revealed to be stabilized by elongation of the repeating unit until the degree of the polymerization reaches 80. The slightly influence of temperature on the CD spectra of poly-l-1100 in CHCl3 indicated the helical conformation was quite stable at least in the range of 0–55 °C. Although poly-l-1100 showed similar CD spectra in different aprotic solvents, remarkable decrease was observed upon the addition of protic solvents such as methanol due to the weakened hydrogen bonding interactions between the adjacent repeating units. The poly-l-1100 behaves as a pH-responsive property; the helical structure of the main chain can be transformed to random coil by addition of trifluoroacetic acid to the THF solution which again switches back to helical conformation by neutralization with triethylamine. It was confirmed that the copolymerization of l-1 and d-1 obeyed the majority rule as supported by the nonlinear correlation between the enantiomeric excess of monomer 1 with the CD intensities of the generated copolymers. Atomic force microscope (AFM) and scanning electron microscope (SEM) studies revealed poly-l-1100 self-assembled into well-defined helical fibrils with distinct handedness.
研究领域:
有机化学
·
高分子化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
ENZYME AND MICROBIAL TECHNOLOGY
·
2024
·
IF 3.4
Quan Luo,Guan Zhou,Zhongxia Li,Jiangpeng Dong,Hang Zhao,Huifang Xu,Xuefeng Lu
The chiral amine ( R )-2-(1-aminoethyl)-4-fluorophenol has attracted increasing attentions in recent years in the field of pharmaceuticals because of its important use as a building block in the synthesis of novel anti-tumor drugs targeting tropomyosin receptor kinases. In the present study, a ω-transaminase (ωTA) library consisting of 21 ( R )-enantioselective enzymes was constructed and screened for the asymmetric biosynthesis of ( R )-2-(1-aminoethyl)-4-fluorophenol from its prochiral ketone. Using ( R )-α-methylbenzylamine, D-alanine, or isopropylamine as amino donor, 18 ωTAs were identified with target activity and the enzyme AbTA, which was originally identified from Arthrobacter sp. KNK168, was found to be a potent candidate. The E. coli whole cells expressing AbTA could be used as catalysts. The optimal temperature and pH for the activity were 35–40 °C and pH8.0, respectively. Simple alcohols (such as ethanol, isopropanol, and methanol) and dimethyl sulfoxide were shown to be good cosolvents. High activities were detected when using ethanol and dimethyl sulfoxide at the concentrations of 5–20%. In the scaled-up reaction of 1-liter containing 13 mM ketone substrate, about 50% conversion was achieved in 24 h. 6.4 mM ( R )-2-(1-aminoethyl)-4-fluorophenol was generated. After a simple and efficient process of product isolation and purification (with 98.8% recovery), 0.986 g yellowish powder of the product ( R )-2-(1-aminoethyl)-4-fluorophenol with high ( R )-enantiopurity (up to 100% enantiomeric excess) was obtained. This study established an overall process for the biosynthesis of the high value pharmaceutical chiral amine ( R )-2-(1-aminoethyl)-4-fluorophenol by ωTA. Its applicable potential was exemplified by gram-scale production.
研究领域:
生物化学
·
制药工程
·
酶催化
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Catalysis
·
2025
·
IF 4.9
Meichen Zhu,Qinzhe Lin,Mengning Zhong,Jian Dong,Leyi Zhao,Qiyun Wu,Huilin Ren,Wenting Du,Jun Li
Chiral amines serve as vital building blocks in pharmaceutical synthesis, yet their stereoselective production remains a significant challenge. Biocatalytic approaches harness the inherent stereospecificity of enzymes to enable precise, sustainable, and highly selective construction of stereocenters. Here, we engineer an imine reductase (IRED) to catalyze the asymmetric synthesis of (3 S )-3-{[(1 R )-1-(naphthalen-1-yl)ethyl]amino}-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine, the key chiral intermediate of Evocalcet . Computational enzyme design of PcIRED-M3 identified the W219L variant, which enhanced catalytic efficiency 8.9-fold and achieved >99 % diastereomeric excess ( d.e. ) versus 63.15 % in wild-type. The W219L substitution presumably reduces steric hindrance by extending the residue-substrate naphthyl distance from 2.1 Å to 4.7 Å while concurrently improving hydride transfer efficiency. This improvement is also owing to the optimized π-σ orbital alignment with the decreased spacing (from 6.2 Å to 4.9 Å) between the imine carbon and the C-4 position of NADPH’s nicotinamide ring. Reaction parameters optimization (30 % DMSO, K 2 HPO 4 -KH 2 PO 4 buffer pH 7.5, 35 °C) achieved 62.7 % conversion in 48 h. This work establishes the first enzymatic route to Evocalcet intermediates and identifies W219 as a stereochemical gatekeeper residue that allosterically coordinates substrate-cofactor geometry.
研究领域:
生物催化
·
酶工程
·
有机合成
·
药物化学
·
计算酶设计
✓ 已验证
产品关联
DOI
高影响因子
Molecular Catalysis
·
2024
·
IF 3.9
Xiangyu Zheng,Zhe Dou,Wenqiang Xiang,Wen Zhang,Ye Ni,Guochao Xu
N -substituted β-amino esters as an important class of chiral amines, are widely used as building blocks in pharmaceuticals. A novel imine reductase Sv IRED was identified through gene mining from Streptomyces viridochromogenes with high enantioselectivity of > 99 % ee (1 R , 2 S ), 95 % de ( cis:trans ), towards 2-oxocyclohexane-1-carboxylate and cyclopropylamine. Sv IRED exhibited the highest activity at pH 7.0 and 40 °C. A variety of amine donors could be used by Sv IRED and produce chiral N -substituted β-amino esters with different enantioselectivity. Employing methylamine ( i ) and pyrrolidine ( n ) as amine donors, Sv IRED exhibited reversed enantioselectivity of 23 % ee (1 S , 2 R ) and 79 % ee (1 S , 2 R ) respectively. Through alanine scanning, M183 and H244 were identified with remarkable roles in governing enantioselectivity towards i and n . Compared with WT Sv IRED, the enantioselectivity of M183A was inverted to ee value of >99 % (1 R , 2 S ) and de value of >99 % ( cis:trans ) towards i , and the enantioselectivity of H244A was inverted to ee value of 88 % (1 R , 2 S ) and de value of >99 % ( cis:trans ) towards n . Interaction analysis indicated the orientation of ester group was vital for manipulation of enantioselectivity. This study provides novel Imine reductase mutants for enantioselective synthesis of N -substituted β -amino esters with different amine donors.
研究领域:
生物化学
·
生物催化
·
酶工程
·
手性合成
·
药物化学
✓ 已验证
DOI
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2015
·Vol. 100
·期 7
·3101-3111
·
IF 3.337
Chen Yujie,Yi Dong,Jiang Shuiqin,Wei Dongzhi
ω-Transaminases (ω-TAs) are one of the most popular candidate enzymes in the biosynthesis of chiral amines. Determination of yet unidentified ω-TAs is important to broaden their potential for synthetic application. Taurine–pyruvate TA (TPTA, EC 2.6.1.77) is an ω-TA belonging to class III of TAs. In this study, we cloned a novel thermostable TPTA from Geobacillus thermodenitrificans (TPTA gth ) and overexpressed it in Escherichia coli . The enzyme showed the highest activity at pH 9.0 and 65 °C, with remarkable thermostability and tolerance toward organic solvents. Its K
M and v
max values for taurine were 5.3 mM and 0.28 μmol s −1 mg −1 , respectively. Determination of substrate tolerance indicated its broad donor and acceptor ranges for unnatural substrates. Notably, the enzyme showed relatively good activity toward ketoses, suggesting its potential for catalyzing the asymmetric synthesis of chiral amino alcohols. The active site of TPTA gth was identified by performing protein sequence alignment, three-dimensional structure simulation, and coenzyme pyridoxamine phosphate docking. The protein sequence and structure of TPTA gth were similar to those of TAs belonging to the 3N5M subfamily. Its active site was found to be its special large pocket and substrate tunnel. In addition, TPTA gth showed a unique mechanism of sulfonate/α-carboxylate recognition contributed by Arg163 and Gln160. We also determined the protein sequence fingerprint of TPTAs in the 3N5M subfamily, which involved Arg163 and Gln160 and seven additional residues from 413 to 419 and lacked Phe/Tyr22, Phe85, and Arg409.
研究领域:
生物催化
·
酶学
·
手性化学
·
蛋白质工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）