23357-45-1Relevant academic research and scientific papers
Benzocycloarene hydroxylation by P450 biocatalysis
Mayhew, Martin P.,Roitberg, Adrian E.,Tewari, Yadu,Holden, Marcia J.,Vanderah, David J.,Vilker, Vincent L.
, p. 35 - 42 (2002)
Experimental and theoretical studies of the hydroxylation of a family of benzocycloarene compounds [benzocyclobutene, benzocyclopentene (indan), benzocyclohexene (tetralin), and benzocycloheptene] by wild type and Y96F mutant P450cam were performed in order to understand the factors affecting product distribution, catalytic rate and cofactor utilization. The products of all reactions except that of benzocycloheptene were regiospecifically hydroxylated in the 1-position. Reaction energetics predominated over active site steric constraints in this case so that quantum mechanical calculations (B3LYP/6-31G*) comparing the energetics of all possible radical intermediates successfully predicted hydroxylation at the 1- and 3-positions of benzocycloheptene, and at the 1-position for the other three compounds. However, the fact that the ratio of 1-alcohol to 3-alcohol changes significantly between wild type and Y96F mutant P450cam indicates that active site geometry and composition also play a significant role in determining BCA7 product regiospecificity. The indan and tetralin reaction products were stereoselective for the R enantiomer (88 and 94%, respectively). Steric constraints of the active site were confirmed by molecular dynamics calculations (locally enhanced sampling dynamics) to control enantiomer distribution for tetralin hydroxylation. NADH coupling, binding affinity, and product turnover rates were dramatically higher for Y96F P450cam, showing that the removal of the active site hydroxyl group on tyrosine makes the enzyme better suited for oxidation of these hydrophobic compounds. NADH coupling, binding affinity and product turnover rate for each enzyme generally increased with arene ring size. For both enzymes, NADH coupling and product turnover rates were correlated with the extent of high-spin shift upon substrate binding as determined by the shift in Soret absorption bands at 417 and 391 nm.
Improving the enantioselectivity of artificial transfer hydrogenases based on the biotin-streptavidin technology by combinations of point mutations
Pordea,Creus,Letondor,Ivanova,Ward
, p. 601 - 604 (2010)
Artificial metalloenzymes based on the incorporation of biotinylated ruthenium piano-stool complexes within streptavidin can be readily optimized by chemical or genetic means. We performed genetic modifications of such artificial metalloenzymes for the tr
Enantioselective benzylic hydroxylation of indan and tetralin with Pseudomonas monteilii TA-5
Lie, Felicia,Chen, Yongzheng,Wang, Zunsheng,Li, Zhi
, p. 1206 - 1211 (2009)
A set of 22 toluene- and ethylbenzene-degrading strains were screened for the enantioselective benzylic hydroxylation of indan and tetralin, and Pseudomonas monteilii TA-5 was discovered as an active and selective biocatalyst for such hydroxylations. Cells of P. monteilii TA-5 can be easily grown to a high density and demonstrated a specific hydroxylation activity of 24 U/g cdw (cell dry weight). Conditions for the hydroxylation of indan 1a and tetralin 1b with resting cells of this strain were optimized, to give the corresponding (R)-1-indanol 2a and (R)-1-tetralol 2b in 99% ee and 62-67% yields, respectively. No significant product inhibition was observed, and biohydroxylation with cell-free extracts suggested that the responsible hydroxylase is a soluble enzyme depending on either NADH or NADPH. Preparative biohydroxylation was demonstrated with resting cells as biocatalysts, affording (R)-2a in 99% ee and 65% yield, and (R)-2b in 99% ee and in 63% yield, respectively.
Concurrent oxidations with tandem biocatalysts in one pot: Green, selective and clean oxidations of methylene groups to ketones
Zhang, Wei,Tang, Weng Lin,Wang, Daniel I. C.,Li, Zhi
, p. 3284 - 3286 (2011)
A novel tandem-biocatalysts system consisting of a monooxygenase-containing microorganism and an alcohol dehydrogenase is developed for the concurrent oxidations of methylene groups to ketones in one pot, providing green, clean and simple access to valuable ketones with high yield, excellent selectivity and efficient cofactor recycling.
CH-activating oxidative hydroxylation of 1-tetralones and related compounds with high regio- and stereoselectivity
Roiban, Gheorghe-Doru,Agudo, Rubn,Ilie, Adriana,Lonsdale, Richard,Reetz, Manfred T.
, p. 14310 - 14313 (2014)
Mutants of P450-BM3 evolved by directed evolution are excellent catalysts in the CH-activating oxidative hydroxylation of 1-tetralone derivatives and of indanone, with unusually high regio- and enantioselectivity being observed. Similar results were achieved in the oxidative hydroxylation of tetralin and indane. The products are useful building blocks in the synthesis of a number of biologically active compounds.
Designer Outer Membrane Protein Facilitates Uptake of Decoy Molecules into a Cytochrome P450BM3-Based Whole-Cell Biocatalyst
Karasawa, Masayuki,Shoji, Osami,Stanfield, Joshua Kyle,Suzuki, Kazuto,Yonemura, Kai
supporting information, (2021/12/16)
We report an OmpF loop deletion mutant, which improves the cellular uptake of external additives into an Escherichia coli whole-cell biocatalyst. Through co-expression of the OmpF mutant with wild-type P450BM3 in the presence of decoy molecules, the yield
A NEW TEMPLATE of MITSUNOBU ACYLATE CLEAVABLE in NONALKALINE CONDITIONS
Sai, Yusuke,Sakakibara, Yoshimichi,Shigetomi, Kengo,Ubukata, Makoto,Uraki, Yasumitsu
, p. 140 - 158 (2022/01/08)
The Mitsunobu inversion is one of the reliable methods for stereospecific substitution of chiral alcohols, but its deacylation step has limited the substrate scope. Here, we propose a new template of the Mitsunobu acylate that can be deacylated in non-alkaline treatments. The 3,4-dihydroxy-2-methylenebutanoate was selected as a template structure, and its acetonide- or bisTBS derivatives were synthesized. The latter especially showed excellent inversion efficiency (up to >99% ee) and good elimination performance for a series of secondary alcohols in near-neutral conditions. The results demonstrated the applicability of the new template for the substrates labile in alkaline conditions, such as a-hydroxyesters.
Chiral Yolk-Shell MOF as an Efficient Nanoreactor for Asymmetric Catalysis in Organic-Aqueous Two-Phase System
Shi, Shunli,Zhong, Yicheng,Hu, Zhuo,Wang, Lei,Yuan, Mingwei,Ding, Shunmin,Wang, Shuhua,Chen, Chao
supporting information, p. 12714 - 12718 (2021/09/11)
It remains a great challenge to introduce large and efficient homogeneous asymmetric catalysts into MOFs and other microporous materials as well as retain their degrees of freedom. Herein, a new heterogeneous strategy of homogeneous chiral catalysts is proposed, that is, to construct a yolk-shell MOFs-confined, large-size, and highly efficient homogeneous chiral catalyst, which can be used as a nanoreactor for asymmetric catalytic reactions.
Enantioselective Hydroxylation of Benzylic C(sp3)-H Bonds by an Artificial Iron Hydroxylase Based on the Biotin-Streptavidin Technology
Barnet, Maxime,Peterson, Ryan L.,Rebelein, Johannes G.,Rumo, Corentin,Serrano-Plana, Joan,Ward, Thomas R.
supporting information, p. 10617 - 10623 (2020/07/04)
The selective hydroxylation of C-H bonds is of great interest to the synthetic community. Both homogeneous catalysts and enzymes offer complementary means to tackle this challenge. Herein, we show that biotinylated Fe(TAML)-complexes (TAML = Tetra Amido Macrocyclic Ligand) can be used as cofactors for incorporation into streptavidin to assemble artificial hydroxylases. Chemo-genetic optimization of both cofactor and streptavidin allowed optimizing the performance of the hydroxylase. Using H2O2 as oxidant, up to ～300 turnovers for the oxidation of benzylic C-H bonds were obtained. Upgrading the ee was achieved by kinetic resolution of the resulting benzylic alcohol to afford up to >98% ee for (R)-tetralol. X-ray analysis of artificial hydroxylases highlights critical details of the second coordination sphere around the Fe(TAML) cofactor.
Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization
Zhang, Wuyuan,Fueyo, Elena Fernandez,Hollmann, Frank,Martin, Laura Leemans,Pesic, Milja,Wardenga, Rainer,H?hne, Matthias,Schmidt, Sandy
, p. 80 - 84 (2019/01/04)
In this study, we combined photo-organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo-organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light-driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α-chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two-phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo-organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale.
