128949-50-8

Upstream product

• 1746-13-0 allyl phenyl ether 
• 4437-83-6 4-(phenoxy)methyl-1,3-dioxolane-2-one 
• 122-60-1 Phenyl glycidyl ether 
• 538-43-2 3-phenoxy-1,2-propanediol 
• 184343-68-8 (R)-4-(phenoxymethyl)-1,3-dioxolan-2-one 
• 556-52-5 oxiranyl-methanol 
• 108-95-2 phenol 
• 71031-03-3 (R)-phenyl glycidyl ether 
• 170375-42-5 (RS)-1-tert-butyldimethylsilyloxy-3-phenoxy-2-propanol 
• 57044-25-4 (R)-oxiranemethanol 
• 60456-23-7 (S)-oxiranemethanol 
• 206259-32-7 (4R,5R)-2-chloro-N,N,N',N'-tetramethyl-1,3,2-dioxaphospholane-4,5-dicarboxamide 
• 296269-89-1 1-hydroxy-3-phenoxy-2-propanone 
• 82430-37-3 (R)-2,2-dimethyl-4-(phenoxymethyl)-1,3-dioxolane 

Downstream Products

• 140630-40-6 Acetic acid (R)-1-bromomethyl-2-phenoxy-ethyl ester 
• 106351-44-4 (2S)-1-Isopropylamino-3-phenoxy-2-propanol 
• 71031-03-3 (R)-phenyl glycidyl ether 
• 106052-97-5 (R)-2-Methoxy-2-methyl-4-phenoxymethyl-[1,3]dioxolane 

Relevant academic research and scientific papers

Highly enantioselective resolution of terminal epoxides using polymeric catalysts

Poly-salen-Co(III) complexes were employed in the hydrolytic kinetic resolution (HKR) of terminal epoxides and ee's up to 98% were obtained. In the HKR of epichlorohydrin, the polymeric catalysts can be recovered and modified for recycling. The recovered

Enantioselective catalysis and analysis on a chip

A chip off the old block: A prototype of a miniaturized catalysis laboratory is successfully applied for screening enantioselective biocatalysts created by directed evolution of enzymes. For this purpose an integrated microfluidic catalysis/analysis chip has been developed (see scheme SO: sample outlet, SI: alternative sample inlet, BI: buffer outlet). (Chemical Equation Presented)

Enhancing the Enantioselectivity of an Epoxide Hydrolase by Directed Evolution

(Matrix presented) The epoxide hydrolase (EH) from Aspergillus niger, which shows a selectivity factor of only E = 4.6 in the hydrolytic kinetic resolution of glycidyl phenyl ether, has been subjected to directed evolution for the purpose of enhancing enantioselectivity. After only one round of error-prone polymerase chain reaction (epPCR), enantioselectivity was more than doubled (E = 10.8). The improved mutant enzyme contains three amino acid exchanges, two of which are spatially far from the catalytically active center.

Enhancing the thermal robustness of an enzyme by directed evolution: Least favorable starting points and inferior mutants can map superior evolutionary Pathways

In a previous directed evolution study, the B-FIT approach to increasing the thermal robustness of proteins was introduced and applied to the lipase from Bacillus subtilis. It is based on the general concept of iterative saturation mutagenesis (ISM), according to which sites in an enzyme are subjected to saturation mutagenesis, the best hit of a given library is then used as a template for randomization at other sites, and the process is continued until the desired catalyst improvement has been achieved. The appropriate choice of the ISM sites is crucial; in the B-FIT method the criterion is residues characterized by highest B factors available from X-ray crystallography data. In the present study, B-FIT was employed in order to increase the thermal robustness of the epoxide hydrolase from Aspergillus niger. Several rounds of ISM resulted in the best variant showing a 21 °C increase in the T 6050 value, an 80-fold improvement in half-life at 60 °C, and a 44 kcalmol-1 improvement in inactivation energy. Seven other variants were also evolved with moderate yet significant improvements; these were characterized by 10-14°C increases in T 6050, 20-30-fold improvement in half-lives at 60°C and 15-20 kcalmol-1 elevations in activation energy. Unexpectedly, in the ISM process the best variants were obtained from essentially neutral or even inferior mutant parents, that is, when a given library contains no improved mutants. This constitutes a practical way to escape from what appear to be local minima (" dead ends" ) in the fitness landscape- a finding of notable significance in directed evolution.

Asymmetric ring opening of terminal epoxides via kinetic resolution catalyzed by chiral (salen)Co mixture

The highly enantioselective hydrolytic kinetic resolution (HKR) of racemic terminal epoxides by bimetallic chiral (salen)Co and (salen)Co(III)-OAc mixture provides a simple and effective method for the synthesis of enantiomerically enriched terminal epoxides (ee > 99%) and diols. At the equimolar amounts of bimetallic chiral (salen)Co and (salen)Co(II)-OAc, the catalytic activity increases more than two times in comparison with (salen)Co(III)-OAc used alone. The mixed catalytic system can be recycled and reused. No significant loss of catalytic activity was observed after three runs.

Enhanced cooperative activation effect in the hydrolytic kinetic resolution of epoxides on [co(salen)] catalysts confined in nanocages

(Chemical Equation Presented) Being cagey: More than two chiral [Co-(salen)] catalyst molecules can be confined in one nanocage of SBA-16 by reducing the pore entrance size by silylation. The [Co(salen)]/SBA-16 catalysts with more than two [Co(salen)] complexes in each cage show a significantly enhanced cooperative activation effect and exhibit much higher activity than the homogeneous [Co(salen)] catalyst in the hydrolytic kinetic resolution of epoxides (see scheme).

Directed evolution of enantioselective enzymes: Iterative cycles of CASTing for probing protein-sequence space

(Chemical Equation Presented) ReCASTing for success: The recently introduced method of combinatorial active-site saturation test (CAST) has been applied in iterative cycles in the directed evolution of enantioselective wild-type epoxide hydrolases (WT-EH).

Enhancing the efficiency of directed evolution in focused enzyme libraries by the adaptive substituent reordering algorithm

Directed evolution is a broadly successful strategy for protein engineering in the quest to enhance the stereoselectivity, activity, and thermostability of enzymes. To increase the efficiency of directed evolution based on iterative saturation mutagenesis, the adaptive substituent reordering algorithm (ASRA) is introduced here as an alternative to traditional quantitative structure-activity relationship (QSAR) methods for identifying potential protein mutants with desired properties from minimal sampling of focused libraries. The operation of ASRA depends on identifying the underlying regularity of the protein property landscape, allowing it to make predictions without explicit knowledge of the structure-property relationships. In a proof-of-principle study, ASRA identified all or most of the best enantioselective mutants among the synthesized epoxide hydrolase from Aspergillus niger, in the absence of peptide seeds with high E-values. ASRA even revealed a laboratory error from irregularities of the reordered E-value landscape alone.

Highly regio- and enantio-selective hydrolysis of two racemic epoxides by GmEH3, a novel epoxide hydrolase from Glycine max

A novel epoxide hydrolase from Glycine max, designated GmEH3, was excavated based on the computer-aided analysis. Then, gmeh3, a GmEH3-encoding gene, was cloned and successfully expressed in E. coli Rosetta(DE3). Among the ten investigated rac-epoxides, GmEH3 possessed the highest and best complementary regioselectivities (regioselectivity coefficients, αS = 93.7% and βR = 97.2%) in the asymmetric hydrolysis of rac-m-chlorostyrene oxide (5a), and the highest enantioselectivity (enantiomeric ratio, E = 55.6) towards rac-phenyl glycidyl ether (7a). The catalytic efficiency (kcatS/KmS = 2.50 mM?1 s?1) of purified GmEH3 for (S)-5a was slightly higher than that (kcatR/KmR = 1.52 mM?1 s?1) for (R)-5a, whereas the kcat/Km (5.16 mM?1 s?1) for (S)-7a was much higher than that (0.09 mM?1 s?1) for (R)-7a. Using 200 mg/mL wet cells of E. coli/gmeh3 as the biocatalyst, the scale-up enantioconvergent hydrolysis of 150 mM rac-5a at 25 °C for 1.5 h afforded (R)-5b with 90.2% eep and 95.4% yieldp, while the kinetic resolution of 500 mM rac-7a for 2.5 h retained (R)-7a with over 99% ees and 43.2% yields. Furthermore, the sources of high regiocomplementarity of GmEH3 for (S)- and (R)-5a as well as high enantioselectivity towards rac-7a were analyzed via molecular docking (MD) simulation.

Enantioselective Resolution Copolymerization of Racemic Epoxides and Anhydrides: Efficient Approach for Stereoregular Polyesters and Chiral Epoxides

Herein we report an efficient strategy for preparing isotactic polyesters and chiral epoxides via enantioselective resolution copolymerization of racemic terminal epoxides with anhydrides, mediated by enantiopure bimetallic complexes in conjunction with a nucleophilic cocatalyst. The chirality of both the axial linker and the diamine backbones of the ligand are responsible for the chiral induction of this kinetic resolution copolymerization process. The catalyst systems exhibit exceptional levels of enantioselectivity with a kinetic resolution coefficient exceeding 300 for various racemic epoxides, affording highly isotactic copolymers (selectivity factors of more than 300) with a completely alternating structure and low polydispersity index. Most of the produced isotactic polyesters are typical semicrystalline materials with melting temperatures in the range from 77 to 160 °C.