- Structure of the fungal hydroxylase, CYP505A30, and rational transfer of mutation data from CYP102A1 to alter regioselectivity
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CYP505A30 is a fungal, self-sufficient cytochrome P450 monooxygenase that can selectively oxyfunctionalisen-alkanes, fatty alcohols, and fatty acids. From alkanes, it produces a mixture of non-vicinal diols by two sequential hydroxylation reactions. Here we report the structure of the haem domain of CYP505A30, the first structure for a member of the CYP505 family, with dodecanoic acid bound within the active site. Overall, a high structural similarity to the related bacterial CYP102A1 was observed, despite low sequence identity (a high degree of conservation with only two amino acid differences close to the haem. Stabilisation of the fatty acid substrate in CYP505A30 also occurs, as in CYP102A1,viaan arginine residue. However, compared to R47, which is situated in the β1 region of CYP102A1, R358 is located in the β3 region of CYP505A30. We furthermore created mutants to test if it is possible to rationally transfer the knowledge on active site mutations in CYP102A1 to change the regioselectivity of CYP505A30. The introduction of F93V, I334F mutations resulted in increased ω-1 (C2) regioselectivity, similar to CYP102A1 87-328, of more than 80% forn-octane and 90% forn-decane. Changing residues to resemble the CYP102A1 wildtype increased the regioselectivity towards ω-2 (C3) to over 60% for both substrates. The knowledge gained from this study unlocks a more selective production of symmetrical non-vicinal diols fromn-alkanes.
- Aschenbrenner, Jasmin C.,Ebrecht, Ana C.,Opperman, Diederik J.,Smit, Martha S.,Tolmie, Carmien
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p. 7359 - 7367
(2021/11/23)
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- Biocatalytic synthesis of non-vicinal aliphatic diols
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Biocatalysts are receiving increased attention in the field of selective oxyfunctionalization of C-H bonds, with cytochrome P450 monooxygenases (CYP450s), and the related peroxygenases, leading the field. Here we report on the substrate promiscuity of CYP505A30, previously characterized as a fatty acid hydroxylase. In addition to its regioselective oxyfunctionalization of saturated fatty acids (ω-1-ω-3 hydroxylation), primary fatty alcohols are also accepted with similar regioselectivities. Moreover, alkanes such as n-octane and n-decane are also readily accepted, allowing for the production of non-vicinal diols through sequential oxygenation. This journal is
- Ebrecht, Ana C.,Aschenbrenner, Jasmin C.,Smit, Martha S.,Opperman, Diederik J.
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supporting information
p. 439 - 445
(2021/01/29)
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- Ruthenium-Catalyzed Selective Hydrogenation of Epoxides to Secondary Alcohols
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A ruthenium(II)-catalyzed highly selective Markovnikov hydrogenation of terminal epoxides to secondary alcohols is reported. Diverse substitutions on the aryl ring of styrene oxides are tolerated. Benzylic, glycidyl, and aliphatic epoxides as well as diepoxides also underwent facile hydrogenation to provide secondary alcohols with exclusive selectivity. Metal-ligand cooperation-mediated ruthenium trans-dihydride formation and its reaction involving oxygen and the less substituted terminal carbon of the epoxide is envisaged for the origin of the observed selectivity.
- Thiyagarajan, Subramanian,Gunanathan, Chidambaram
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supporting information
p. 9774 - 9778
(2019/12/02)
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- Electrochemical Coupling of Biomass-Derived Acids: New C8 Platforms for Renewable Polymers and Fuels
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Electrolysis of biomass-derived carbonyl compounds is an alternative to condensation chemistry for supplying products with chain length >C6for biofuels and renewable materials production. Kolbe coupling of biomass-derived levulinic acid is used to obtain 2,7-octanedione, a new platform molecule only two low process-intensity steps removed from raw biomass. Hydrogenation to 2,7-octanediol provides a chiral secondary diol largely unknown to polymer chemistry, whereas intramolecular aldol condensation followed by hydrogenation yields branched cycloalkanes suitable for use as high-octane, cellulosic gasoline. Analogous electrolysis of an itaconic acid-derived methylsuccinic monoester yields a chiral 2,5-dimethyladipic acid diester, another underutilized monomer owing to lack of availability.
- Wu, Linglin,Mascal, Mark,Farmer, Thomas J.,Arnaud, Sacha Pérocheau,Wong Chang, Maria-Angelica
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p. 166 - 170
(2017/01/17)
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- Regioselective reductive hydration of alkynes to form branched or linear alcohols
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The regioselective reductive hydration of terminal alkynes using two complementary dual catalytic systems is described. Branched or linear alcohols are obtained in 75-96% yield with ?25:1 regioselectivity from the same starting materials. The method is compatible with terminal, di-, and trisubstituted alkenes. This reductive hydration constitutes a strategic surrogate to alkene oxyfunctionalization and may be of utility in multistep settings.
- Li, Le,Herzon, Seth B.
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supporting information
p. 17376 - 17379,4
(2020/09/16)
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- Magnetically separable Pd catalyst for highly selective epoxide hydrogenolysis under mild conditions
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A magnetically separable palladium catalyst was synthesized simply through a sol-gel process incorporating palladium nanoparticles and superparamagnetic iron oxide nanoparticles in aluminum oxyhydroxide matrix, which is highly active and selective for epoxide hydrogenolysis at room temperature under 1 atm H 2. The catalyst was recycled for 25 times without loss of the activity.
- Kwon, Min Serk,Park, In Soo,Jang, Jum Suk,Lee, Jae Sung,Park, Jaiwook
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p. 3417 - 3419
(2008/02/12)
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- Iterative tandem catalysis of secondary diols and diesters to chiral polyesters
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The well-known dynamic kinetic resolution of secondary alcohols and esters was extended to secondary diols and diesters to afford chiral polyesters. This process is an example of iterative tandem catalysis (ITC), a polymerization method where the concurrent action of two fundamentally different catalysts is required to achieve chain growth. In order to procure chiral polyesters of high enantiomeric excess value (ee) and good molecular weight, the catalysts employed need to be complementary and compatible during the polymerization reaction. We here show that Shvo's catalyst and Novozym 435 fulfil these requirements. The optimal polymerization conditions of 1,1′-(1,3-phenylene) diethanol (1,3-diol) and diisopropyl adipate required 2mol% Shvo's catalyst and 12 mg Novozym 435 per mmol alcohol group in the presence of 0.5 M 2,4-dimethyl-3- pentanol as the hydrogen donor. With these conditions, chiral polyesters were obtained with peak molecular weights up to 15kDa, an ee value up to 99% and with 1-3% ketone end groups. Also with the structural isomer, 1,4-diol, a chiral polyester was obtained, albeit with lower molecular weight (8.3 kDa) and slightly lower ee (94%). Aliphatic secondary diols also resulted in enantio-enriched polymers but at most an ee of 46% was obtained with molecular weights in the range of 3.33.7 kDa. This low ee originates from the intrinsic low enantioselectivity of Novozym 435 for this type of secondary aliphatic diols. The results presented here show that ITC can be applied to procure chiral polyesters with good molecular weight and high ee from optically inactive AA-BB type monomers.
- Van As, Bart A.C.,Van Buijtenen, Jeroen,Mes, Tristan,Palmans, Anja R.A.,Meijer
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p. 8325 - 8332
(2008/09/16)
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- A convenient one-pot synthesis of cyclohexenic primary amines
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The reaction between Grignard reagents prepared from allylic or propargylic halides and the N-phenylsulfenimine derived from the heptane- 2,6-dione affords primary 1-alkenyl (or alkynyl)-3-methylcyclohex-2-enamines in good yields.
- Barbot, Francis,Aidene, Mohand,Miginiac, Leone
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p. 3279 - 3289
(2007/10/03)
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- Meerwein Reduction of Levulinic Acid Derivatives: A New Route for the Synthesis of Glutamic Acid
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Glutamic acid has been prepared from levulinic acid by a new route.In this method α-ketoglutaric (III) acid is obtained by oxidation of δ-benzallevulinic acid (II) and converted into diethyl ester (IV) which on Meerwein-Pondorff-Verley reduction furnishes the hydroxy derivative (V).The latter (V) is converted into chloro derivative (VI) which on amination gives glutamic acid (VII) in a good yield.Meerwein-Pondorff-Verley reduction of ethyl levulinate, ethyl β-bromolevulinate and 2,7-octanedione has also been studied.However, such a reduction of ethyl β-aminolevulinate remains unsuccessfull.
- Joshi, Uday R.,Limaye, P. A.
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p. 1176 - 1178
(2007/10/02)
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