4221-99-2Relevant academic research and scientific papers
Enhancing enantioselectivity of Candida antarctica lipase B towards chiral sec-alcohols bearing small substituents through hijacking sequence of A homolog
Yi, Seonghyeon,Park, Seongsoon
, (2021)
Candida antarctica lipase B (CAL-B) exhibits extraordinary enantioselectivity towards most chiral sec-alcohols but not towards sec-alcohols bearing substituents smaller than a propyl group (i.e., (±)-but-3-yn-2-ol (E = 4) and (±)-butan-2-ol (E = 7)). Previously, we reported a homologous enzyme (lipase from Pseudozyma brasiliensis GHG001, PBL) of CAL-B, which exhibited high enantioselectivity of CAL-B towards (±)-but-3-yn-2-ol (E > 200). Based on the result, we hypothesized that the comparison of their local sequence or structure would provide a clue for enhancing the enantioselectivity of CAL-B. In this paper, we report enhancing enantioselectivity of CAL-B towards (±)-but-3-yn-2-ol and (±)-butan-2-ol through the substitution of the local sequence of CAL-B with that of PBL. The sequence-substituted mutant of CAL-B exhibited much higher enantioselectivity towards (±)-but-3-yn-2-ol (E > 200) and (±)-butan-2-ol (E > 25).
Stereospecificity of hydrogen transfer by the NAD+-linked alcohol dehydrogenase from the Antarctic psychrophile Moraxella sp. TAE123
Velonia, Kelly,Tsigos, Iason,Bouriotis, Vassilis,Smonou, Ioulia
, p. 65 - 68 (1999)
Investigation of the stereochemistry of the hydride transfer in reactions catalyzed by the recently isolated NAD+-linked alcohol dehydrogenase from the Antarctic psychrophile Moraxella sp. TAE123 was accomplished by using 1H NMR spectroscopy of the deuterated coenzyme. It was found that this new psychrophilic enzyme is a type A dehydrogenase. Moraxella sp. ADH reduces stereospecifically 2-butanone to produce (S)-2-butanol.
Discovery and Redesign of a Family VIII Carboxylesterase with High (S)-Selectivity toward Chiral sec-Alcohols
Park, Areum,Park, Seongsoon
, p. 2397 - 2402 (2022/02/17)
Highly enantioselective lipase has been widely utilized in the preparation of versatile enantiopure chiral sec-alcohols through kinetic or dynamic kinetic resolution. Lipase is intrinsically (R)-selective, and it is difficult to obtain (S)-selective lipase. Recent crystal structures of a family VIII carboxylesterase have revealed that the spatial array of its catalytic triad is the mirror image of that of lipase but with a catalytic triad that is distinct from lipase. We, therefore, hypothesized that the family VIII carboxylesterase may exhibit (S)-enantioselectivity toward sec-alcohols similar to (S)-selective serine protease, whose catalytic triad is also spatially arrayed as its mirror image. In this study, a homologous enzyme (carboxylesterase from Proteobacteria bacterium SG_bin9, PBE) of a known family VIII carboxylesterase (pdb code: 4IVK) was prepared, which showed not only moderate (S)-selectivity toward sec-alcohols such as 3-butyn-2-ol and 1-phenylethyl alcohol but also (R)-selectivity toward particular sec-alcohols among the substrates explored. Furthermore, the (S)-selectivity of PBE has been significantly improved by rational redesign based on molecular modeling. Molecular modeling identified a binding pocket composed of Ser381, Ala383, and Arg408 for the methyl substituent of (R)-1-phenylethyl acetate and suggested that larger residues may increase the enantioselectivity by interfering with the binding of the slow-reacting enantiomer. As predicted, substituting Ser381with larger residues (Phe, Tyr, and Trp) significantly improved the (S)-selectivity of PBE toward all sec-alcohols explored, even the substrates toward which the wild-type PBE exhibits (R)-selectivity. For instance, the enantioselectivity toward 3-butyn-2-ol and 1-phenylethyl alcohol was improved from E = 5.5 and 36.1 to E = 2001 and 882, respectively, by single mutagenesis (S381F).
Novel highly efficient absolute optical resolution method by serial combination of two asymmetric reactions from acetylene monomers having racemic substituents
Aoki, Toshiki,Kaneko, Takashi,Liu, Lijia,Suzuki, Junpei,Tang, Yanan,Teraguchi, Masahiro
supporting information, p. 450 - 461 (2022/01/15)
For general optical resolution, an optical resolution agent is necessary, and the best agent should be selected for each racemic compound. In this study, we will report that a novel optical resolution method by circularly polarized light (CPL) without any
London Dispersion Interactions Rather than Steric Hindrance Determine the Enantioselectivity of the Corey–Bakshi–Shibata Reduction
Eschmann, Christian,Song, Lijuan,Schreiner, Peter R.
, p. 4823 - 4832 (2021/02/01)
The well-known Corey–Bakshi–Shibata (CBS) reduction is a powerful method for the asymmetric synthesis of alcohols from prochiral ketones, often featuring high yields and excellent selectivities. While steric repulsion has been regarded as the key director of the observed high enantioselectivity for many years, we show that London dispersion (LD) interactions are at least as important for enantiodiscrimination. We exemplify this through a combination of detailed computational and experimental studies for a series of modified CBS catalysts equipped with dispersion energy donors (DEDs) in the catalysts and the substrates. Our results demonstrate that attractive LD interactions between the catalyst and the substrate, rather than steric repulsion, determine the selectivity. As a key outcome of our study, we were able to improve the catalyst design for some challenging CBS reductions.
Synthesis of cis-1,2-diol-type chiral ligands and their dioxaborinane derivatives: Application for the asymmetric transfer hydrogenation of various ketones and biological evaluation
Kilic, Ahmet,Balci, Tu?ba Ersayan,Arslan, Nevin,Aydemir, Murat,Durap, Feyyaz,Okumu?, Veysi,Tekin, Recep
, (2020/06/10)
Two cis-1,2-diol-type chiral ligands (T1 and T2) and their tri-coordinated chiral dioxaborinane (T(1–2)B(1–2)) and four-coordinated chiral dioxaborinane adducts with 4-tert-butyl pyridine sustained by N → B dati
Boron containing chiral Schiff bases: Synthesis and catalytic activity in asymmetric transfer hydrogenation (ATH) of ketones
Pa?a, Salih,Arslan, Nevin,Meri??, Nermin,Kayan, Cezmi,Bingül, Murat,Durap, Feyyaz,Aydemir, Murat
, (2019/09/19)
Asymmetric Transfer Hydrogenation (ATH) has been an attractive way for the reduction of ketones to chiral alcohols. A great number of novel and valuable synthetic pathways have been achived by the combination usage of organometallic and coordination chemistry for the production of important class of compounds and particularly optically active molecules. For this aim, four boron containing Schiff bases were synthesized by the reaction of 4-formylphenylboronic acid with chiral amines. The boron containing structures have been found as stable compounds due to the presence of covalent B–O bonds and thus could be handled in laboratory environment. They were characterized by 1H NMR and FT-IR spectroscopy and elemental analysis and they were used as catalyst in the transfer hydrogenation of ketones to the related alcohol derivatives with high conversions (up to 99%) and low enantioselectivities (up to 22% ee).
Enantioselective transfer hydrogenation of pro-chiral ketones catalyzed by novel ruthenium and iridium complexes of well-designed phosphinite ligand
Arslan, Nevin
, p. 628 - 637 (2020/01/02)
The interaction of [Ru(η6-arene)(μ-Cl)Cl]2 and Ir(η5-C5Me5)(μ-Cl)Cl]2 with a new Ionic Liquid-based phosphinite ligand, [(Ph2PO)-C6H9N2Ph]Cl, (2) gave [Ru((Ph2PO)-C6H9N2Ph)(η6-p-cymene)Cl2]Cl (3), [Ru((Ph2PO)-C6H9N2Ph)(benzene)Cl2]Cl (4) and [Ir((Ph2PO)-C6H9N2Ph)(C5Me5)Cl2]Cl (5), complexes. All the compounds were characterized by a combination of multinuclear NMR and IR spectroscopy as well as elemental analysis. Furthermore, the Ru(II) and Ir(III) catalysts were applied to asymmetric transfer hydrogenation of acetophenone derivatives using 2-propanol as a hydrogen source. The results showed that the corresponding alcohols could be obtained with good activity (up to 55% ee and 99% conversion) under mild conditions. Notably, [Ir((Ph2PO)-C6H9N2Ph)(C5Me5)Cl2]Cl (5) is more active than the other analogous complexes in the transfer hydrogenation (up to 81% ee).
Upcycling a plastic cup: One-pot synthesis of lactate containing metal organic frameworks from polylactic acid
Slater, Benjamin,Wong, So-On,Duckworth, Andrew,White, Andrew J. P.,Hill, Matthew R.,Ladewig, Bradley P.
supporting information, p. 7319 - 7322 (2019/06/27)
Waste PLA can be upcycled to metal organic frameworks of potential high value in a one-pot synthesis scheme, where PLA depolymerisation occurs in situ. Three homochiral lactate based frameworks were successfully synthesised and characterised from PLA as a feed source, including ZnBLD. The chiral separation ability of ZnBLD was maintained.
Structural basis for a highly (S)-enantioselective reductase towards aliphatic ketones with only one carbon difference between side chain
Koesoema, Afifa Ayu,Sugiyama, Yosuke,Xu, Zichang,Standley, Daron M.,Senda, Miki,Senda, Toshiya,Matsuda, Tomoko
, p. 9543 - 9553 (2019/09/16)
Aliphatic ketones, such as 2-butanone and 3-hexanone, with only one carbon difference among side chains adjacent to the carbonyl carbon are difficult to be reduced enantioselectively. In this study, we utilized an acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD) to reduce challenging aliphatic ketones such as 2-butanone (methyl ethyl ketone) and 3-hexanone (ethyl propyl ketone) to their corresponding (S)-alcohols with 94% ee and > 99% ee, respectively. Through crystallographic structure determination, it was suggested that residue Trp288 limit the size of the small binding pocket. Docking simulations imply that Trp288 plays an important role to form a C-H?π interaction for proper orientation of ketones in the pro-S binding pose in order to produce (S)-alcohols. The excellent (S)-enantioselectivity is due to a non-productive pro-R binding pose, consistent with the observation that the (R)-alcohol acts as an inhibitor of (S)-alcohol oxidation.
