213479-90-4Relevant articles and documents
Structure-Guided Regulation in the Enantioselectivity of an Epoxide Hydrolase to Produce Enantiomeric Monosubstituted Epoxides and Vicinal Diols via Kinetic Resolution
Hou, Xiao-Dong,Hu, Bo-Chun,Hu, Die,Lei, Yu-Qing,Rao, Yi-Jian,Wu, Min-Chen,Zhang, Dong
supporting information, p. 1757 - 1761 (2022/03/16)
Structure-guided microtuning of an Aspergillus usamii epoxide hydrolase was executed. One mutant, A214C/A250I, displayed a 12.6-fold enhanced enantiomeric ratio (E = 202) toward rac-styrene oxide, achieving its nearly perfect kinetic resolution at 0.8 M in pure water or 1.6 M in n-hexanol/water. Several other beneficial mutants also displayed significantly improved E values, offering promising biocatalysts to access 19 structurally diverse chiral monosubstituted epoxides (97.1 - ≥ 99% ees) and vicinal diols (56.2-98.0% eep) with high yields.
Reprogramming Epoxide Hydrolase to Improve Enantioconvergence in Hydrolysis of Styrene Oxide Scaffolds
Li, Fu-Long,Qiu, Yan-Yan,Zheng, Yu-Cong,Chen, Fei-Fei,Kong, Xu–Dong,Xu, Jian-He,Yu, Hui-Lei
, p. 4699 - 4706 (2020/09/21)
Enantioconvergent hydrolysis by epoxide hydrolase is a promising method for the synthesis of important vicinal diols. However, the poor regioselectivity of the naturally occurring enzymes results in low enantioconvergence in the enzymatic hydrolysis of styrene oxides. Herein, modulated residue No. 263 was redesigned based on structural information and a smart variant library was constructed by site-directed modification using an “optimized amino acid alphabet” to improve the regioselectivity of epoxide hydrolase from Vigna radiata (VrEH2). The regioselectivity coefficient (r) of variant M263Q for the R-isomer of meta-substituted styrene oxides was improved 40–63-fold, and variant M263V also exhibited higher regioselectivity towards the R-isomer of para-substituted styrene oxides compared with the wild type, which resulted in improved enantioconvergence in hydrolysis of styrene oxide scaffolds. Structural insight showed the crucial role of residue No. 263 in modulating the substrate binding conformation by altering the binding surroundings. Furthermore, increased differences in the attacking distance between nucleophilic residue Asp101 and the two carbon atoms of the epoxide ring provided evidence for improved regioselectivity. Several high-value vicinal diols were readily synthesized (>88% yield, 90%–98% ee) by enantioconvergent hydrolysis using the reprogrammed variants. These findings provide a successful strategy for enhancing the enantioconvergence of native epoxide hydrolases through key single-site mutation and more powerful enzyme tools for the enantioconvergent hydrolysis of styrene oxide scaffolds into single (R)-enantiomers of chiral vicinal diols. (Figure presented.).
Kinetic Resolution of 1,2-Diols via NHC-Catalyzed Site-Selective Esterification
Liu, Bin,Yan, Jiekuan,Huang, Ruoyan,Wang, Weihong,Jin, Zhichao,Zanoni, Giuseppe,Zheng, Pengcheng,Yang, Song,Chi, Yonggui Robin
supporting information, p. 3447 - 3450 (2018/06/26)
A kinetic resolution of 1,2-diols bearing both a secondary and a primary alcohol motif through an N-heterocyclic carbene-catalyzed oxidative acylation reaction has been developed. A site- and enantioselective esterification reaction is involved for this process. Both the monoacylated diols obtained and the remaining enantioenriched 1,2-diols are versatile building blocks for the preparation of functional molecules with proven biological activities.
Chiral Ion-Pair Organocatalyst-Promoted Efficient Enantio-selective Reduction of α-Hydroxy Ketones
Zhang, Yiliang,He, Li,Shi, Lei
, p. 1926 - 1931 (2018/03/27)
The enantioselective reduction of α-hydroxy ketones with catecholborane has been developed employing 5 mol% of an 1,1′-bi-2-naphthol (BINOL)-derived ion-pair organocatalyst. This methodology provides a straightforward access to the corresponding aromatic 1,2-diols in high yields (up to 90%) with excellent enantioselectivities (up to 97%). Furthermore, the α-amino ketones also could be reduced with moderate ee values under mild reaction condition. (Figure presented.).
Structurally Defined Molecular Hypervalent Iodine Catalysts for Intermolecular Enantioselective Reactions
Haubenreisser, Stefan,W?ste, Thorsten H.,Martnez, Claudio,Ishihara, Kazuaki,Muiz, Kilian
supporting information, p. 413 - 417 (2016/01/25)
Molecular structures of the most prominent chiral non-racemic hypervalent iodine(III) reagents to date have been elucidated for the first time. The formation of a chirally induced supramolecular scaffold based on a selective hydrogen-bonding arrangement provides an explanation for the consistently high asymmetric induction with these reagents. As an exploratory example, their scope as chiral catalysts was extended to the enantioselective dioxygenation of alkenes. A series of terminal styrenes are converted into the corresponding vicinal diacetoxylation products under mild conditions and provide the proof of principle for a truly intermolecular asymmetric alkene oxidation under iodine(I/III) catalysis.
Production Of Enantiopure alpha-Hydroxy Carboxylic Acids From Alkenes By Cascade Biocatalysis
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Paragraph 0065-0067, (2016/05/02)
The invention provides compositions comprising an alkene epoxidase and a selective epoxide hydrolase, such as a recombinant microorganism comprising a first heterologous nucleic acid encoding an alkene epoxidase and a second heterologous nucleic acid encoding a selective epoxide hydrolase. Exemplary alkene epoxidases include StyAB, while exemplary selective epoxide hydrolases include epoxide hydrolases from Sphingomonas, Solanum tuberosum, or Aspergillus. The invention also provides non-toxic methods of making enantiomerically pure vicinal diols or enantiomerically pure alpha-hydroxy carboxylic acids using these compositions and microorganisms.
Enantioselective Vicinal Diacetoxylation of Alkenes under Chiral Iodine(III) Catalysis
W?ste, Thorsten H.,Mu?iz, Kilian
, p. 816 - 827 (2016/03/15)
A procedure for the intermolecular enantioselective dioxygenation of alkenes under iodine(III) catalysis has been developed. This protocol employs Selectfluor as the terminal oxidant together with a defined C 2-symmetric aryl iodide as the organocatalyst. This enantioselective reaction proceeds under mild conditions and converts a series of terminal and internal styrenes into the corresponding vicinal diacetoxylation products with up to 96% ee.
Transition-Metal-Free Stereospecific Cross-Coupling with Alkenylboronic Acids as Nucleophiles
Li, Chengxi,Zhang, Yuanyuan,Sun, Qi,Gu, Tongnian,Peng, Henian,Tang, Wenjun
supporting information, p. 10774 - 10777 (2016/09/09)
We herein report a transition-metal-free cross-coupling between secondary alkyl halides/mesylates and aryl/alkenylboronic acid, providing expedited access to a series of nonchiral/chiral coupling products in moderate to good yields. Stereospecific SN2-type coupling is developed for the first time with alkenylboronic acids as pure nucleophiles, offering an attractive alternative to the stereospecific transition-metal-catalyzed C(sp2)-C(sp3) cross-coupling.
A broadly applicable and practical oligomeric (salen)Co catalyst for enantioselective epoxide ring-opening reactions
White, David E.,Tadross, Pamela M.,Lu, Zhe,Jacobsen, Eric N.
supporting information, p. 4165 - 4180 (2014/06/09)
The (salen)Co catalyst (4a) can be prepared as a mixture of cyclic oligomers in a short, chromatography-free synthesis from inexpensive, commercially available precursors. This catalyst displays remarkable enhancements in reactivity and enantioselectivity relative to monomeric and other multimeric (salen)Co catalysts in a wide variety of enantioselective epoxide ring-opening reactions. The application of catalyst 4a is illustrated in the kinetic resolution of terminal epoxides by nucleophilic ring-opening with water, phenols, and primary alcohols; the desymmetrization of meso epoxides by addition of water and carbamates; and the desymmetrization of oxetanes by intramolecular ring opening with alcohols and phenols. The favorable solubility properties of complex 4a under the catalytic conditions facilitated mechanistic studies, allowing elucidation of the basis for the beneficial effect of oligomerization. Finally, a catalyst selection guide is provided to delineate the specific advantages of oligomeric catalyst 4a relative to (salen)Co monomer 1 for each reaction class.
Enantioselective trans-dihydroxylation of aryl olefins by cascade biocatalysis with recombinant escherichia coli coexpressing monooxygenase and epoxide hydrolase
Wu, Shuke,Chen, Yongzheng,Xu, Yi,Li, Aitao,Xu, Qisong,Glieder, Anton,Li, Zhi
, p. 409 - 420 (2014/03/21)
Cascade biocatalysis via intracellular epoxidation and hydrolysis was developed as a green and efficient method for enantioselective dihydroxylation of aryl olefins to prepare chiral vicinal diols in high ee and high yield. Escherichia coli (SSP1) coexpressing styrene monooxygenase (SMO) and epoxide hydrolase SpEH was developed as a simple and efficient biocatalyst for S-enantioselective dihydroxylation of terminal aryl olefins 1a-15a to give (S)-vicinal diols 1c-15c in high ee (97.5-98.6% for 10 diols; 92.2-93.9% for 3 diols) and high yield (91-99% for 6 diols; 86-88% for 2 diols; 67% for 3 diols). Combining SMO and epoxide hydrolase StEH showing complementary regioselectivity to SpEH as a biocatalyst for the cascade biocatalysis gave rise to R-enantioselective dihydroxylation of aryl olefins, being the first example of this kind of reversing the overall enantioselectivity of cascade biocatalysis. E. coli (SST1) coexpressing SMO and StEH was also engineered as a green and efficient biocatalyst for R-dihydroxylation of terminal aryl olefins 1a-15a to give (R)-vicinal diols 1c-15c in high ee (94.2-98.2% for 7 diols; 84.2-89.9% for 6 diols) and high yield (90-99% for 6 diols; 85-89% for 5 diols; 65% for 1 diol). E. coli (SSP1) and E. coli (SST1) catalyzed the trans-dihydroxylation of trans-aryl olefin 16a and cis-aryl olefin 17a with excellent and complementary stereoselectivity, giving each of the four stereoisomers of 1-phenyl-1,2- propanediol 16c in high ee and de, respectively. Both strains catalyzed the trans-dihydroxylation of aryl cyclic olefins 18a and 19a to afford the same trans-cyclic diols (1R,2R)-18c and (1R,2R)-19c, respectively, in excellent ee and de. This type of cascade biocatalysis provides a tool that is complementary to Sharpless dihydroxylation, accepting cis-alkene and offering enantioselective trans-dihydroxylation.
