- 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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- CYP505E3: A Novel Self-Sufficient ω-7 In-Chain Hydroxylase
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The self-sufficient cytochrome P450 monooxygenase CYP505E3 from Aspergillus terreus catalyzes the regioselective in-chain hydroxylation of alkanes, fatty alcohols, and fatty acids at the ω-7 position. It is the first reported P450 to give regioselective in-chain ω-7 hydroxylation of C10–C16 n-alkanes, thereby enabling the one step biocatalytic synthesis of rare alcohols such as 5-dodecanol and 7-tetradecanol. It shows more than 70 percent regioselectivity for the eighth carbon from one methyl terminus, and displays remarkably high activity towards decane (TTN≈8000) and dodecane (TTN≈2000). CYP505E3 can be used to synthesize the high-value flavour compound δ-dodecalactone via two routes: 1) conversion of dodecanoic acid into 5-hydroxydodecanoic acid (24 percent regioselectivity), which at low pH lactonises to δ-dodecalactone, and 2) conversion of 1-dodecanol into 1,5-dodecanediol (55 percent regioselectivity), which can be converted into δ-dodecalactone by horse liver alcohol dehydrogenase.
- Maseme, Mpeyake Jacob,Opperman, Diederik Johannes,Pennec, Alizé,Smit, Martha Sophia,van Marwijk, Jacqueline
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supporting information
p. 10359 - 10362
(2020/04/23)
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- ALKANE OXIDATION BY MODIFIED HYDROXYLASES
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This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.
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Paragraph 0323; 0324
(2016/02/16)
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- Revisiting cytochrome P450-mediated oxyfunctionalization of linear and cyclic alkanes
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Cytochrome P450 monooxygenases (CYPs) of the CYP153 family catalyse terminal hydroxylation of n-alkanes. Alkane hydroxylating mutants of self-sufficient CYP102A1 have also been described. We evaluated two CYP153s (a three-component system and a fused self-sufficient CYP), wildtype CYP102A1 and nine CYP102A1 mutants, for the conversion of three cycloalkanes (C6, C7 and C8) and three n-alkanes (C6, C8 and C10) using whole cells (WCs) and crude cell-free extracts (CFEs). The aim was to identify substrate-enzyme combinations that give high product titres and space-time yields (STYs). Comparisons were made using total turnover numbers (TTNs) and turnover frequencies (TOFs) to normalize for CYP expression. Reactions were carried out using high enzyme and substrate concentrations compatible with high STYs. Under these conditions CYP102A1 and the double R47L,Y51F mutant, although not regioselective, performed better on all substrates in terms of product titres over 8 h, and thus STYs and TTNs, than heavily mutated variants that have been reported to give very high TOFs. CYP153A6, with its ferredoxin (Fdx) and ferredoxin reductase (FdR), emerged as the superior catalyst for conversion of n-alkanes. In addition to its excellent regioselectivity it also gave the highest final product titres and STYs in WC conversions of hexane and octane. Interaction with FdR and Fdx initially limited performance in CFEs, but with additional FdR and Fdx gave 1-octanol titres of 50 mmol·LBRM-1 and TTNs exceeding 12,000 over 18 h, rivalling results reported with self-sufficient CYPs. Selecting biocatalysts for application requires caution, since experimental conditions such as amount of substrate added and solubility as well as cofactor dependence and regeneration can have a profound effect on catalyst performance, while stability and efficiency with regard to cofactor usage (coupling efficiency) are at least as important as TOFs when high product titres and STYs are the target.
- Pennec, Aliz,Jacobs, Cheri L.,Opperman, Diederik J.,Smit, Martha S.
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supporting information
p. 118 - 130
(2015/01/30)
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- A novel lipase enzyme panel exhibiting superior activity and selectivity over lipase B from Candida antarctica for the kinetic resolution of secondary alcohols
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A novel, commercially available lipase enzyme panel performing kinetic bioresolutions of a number of secondary alcohols is reported. The secondary alcohols that have been chosen are known from the literature to be particularly challenging substrates to resolve. Following initial screening, four co-solvents were investigated for each lead enzyme in an effort to assess their tolerance to common organic solvents. The superiority of these novel enzymes over lipase B from Candida antarctica (CALB) has been demonstrated.
- O'Neill, Maeve,Beecher, Denis,Mangan, David,Rowan, Andrew S.,Monte, Agnieszka,Sroka, Stefan,Modregger, Jan,Hundle, Bhupinder,Moody, Thomas S.
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experimental part
p. 583 - 586
(2012/08/13)
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- Low-temperature aerobic oxidation of decane using an oxygen-free radical initiator
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The direct selective oxidation of long chain alkanes by O2 is a highly demanding reaction. We have shown that it is possible to oxidise n-decane in the presence of the oxygen-free radical initiator azobisisobutyronitrile. Formation of a range of oxygenated products has been observed under relatively mild conditions (70 °C in air). Although the presence of a catalyst is not essential when the initiator is used, ceria-based catalysts have been found to increase the selectivity to alcohols by modifying the oxyfunctionalisation of decane.
- Lloyd, Rhys,Jenkins, Robert L.,Piccinini, Marco,He, Qian,Kiely, Christopher J.,Carley, Albert F.,Golunski, Stanislaw E.,Bethell, Donald,Bartley, Jonathan K.,Hutchings, Graham J.
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scheme or table
p. 161 - 167
(2011/11/30)
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- Ethynyldiisopropylsilyl: A new alkynylsilane protecting group and click linker
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(Figure presented) A new silyl-based reagent has been developed for catch and release immobilization, combining click chemistry with silyl protection. The traditional all carbon attachment to solid supports in a silyl type linker was substituted with a stable triazole, easily assembled using the CuAAC reaction. The methodology introduces a novel ethynyldiiospropylchlorosilane reagent (EDIPS-Cl) as a functionalized protecting group linker.
- Sharma, Pallavi,Moses, John E.
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supporting information; experimental part
p. 2860 - 2863
(2010/08/20)
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- Regio- And stereoselective subterminal hydroxylations of n-decane by fungi in a liquid-liquid interface bioreactor (L-L IBR)
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This article may be the first report to describe the excellent regio- and stereoselective subterminal hydroxylations of n-alkane with microorganisms. Approximately 2000 fungal strains were screened for the regioselective hydroxylation of n-decane with a s
- Oda, Shinobu,Isshiki, Kunio,Ohashi, Shinichi
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experimental part
p. 105 - 109
(2009/04/10)
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- Titanocene-catalyzed regiodivergent epoxide openings
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The first regiodivergent opening of unbiased epoxides providing the ring-opened products in high enantiomeric excess from racemic and exceptionally high enantiomeric excess from enantioenriched substrates in a double asymmetric process has been devised. It constitutes a more general case of the very important enantioselective openings of meso-epoxides. Copyright
- Gansaeuer, Andreas,Fan, Chun-An,Keller, Florian,Keil, Jutta
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p. 3484 - 3485
(2008/01/01)
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- Stereoselective synthesis of highly enantioenriched (E)-allylsilanes by palladium-catalyzed intramolecular bis-silylation: 1,3-chirality transfer and enantioenrichment via dimer formation
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Highly enantioenriched (E)-allylsilanes have been synthesized from optically active allylic alcohols on the basis of Pd-catalyzed intramolecular bis-silylation followed by highly stereo-specific Si-O elimination reactions. The method involves three steps: 1) O-disilanylation of the allylic alcohols with chlorodisilanes, 2) intramolecular bis-silylation in the presence of a 1,1,3,3-tetramethylbutyl isocyanide/[Pd-(acac)2] (acac = acetylacetonate) catalyst at 110°C, and 3) treatment of the reaction mixture with organolithium reagents. The overall transformation proceeds with nearly complete conservation of the enantiopurity of the starting allyl alcohols by transposition of the C=C bond. For instance, (R)-(E)-3-decen-2-ol (99.6-99.7 % ee) produced (S)-(E)-4-(organosilyl)-2-decene of 98.8-99.4% ee for a variety of silyl groups, including Me3Si, Me2PhSi, tBu-Me 2Si, Et3Si, and iPr3Si. In the bis-silylation step, the initially formed trans-1,2-oxasiletanes immediately dimerize to stereoselectively give 1,5-dioxa-2,6-disilacyclooctanes, which are isolated in high yield by carrying out the reaction at 70C. The eight-membered ring compounds undergo thermal extrusion of (E)-allylsilanes in high yield at 110°C, along with formation of 1,3- dioxa-2,5-disilacyclohexane derivatives. These in turn undergo a Peterson-type elimination by treatment with nucleophiles such as BuLi and PhLi to give the (E)-allylsilanes. All of the steps involved in the sequence proceed with extremely high stereoselectivity and stereospecificity, leading to almost complete 1,3-chirality transfer through the overall transformation. The dimerization step, which forms diastereomeric intermediates, allows the synthesis of a highly enantioenriched allylsilane (99.4% ee) from an optically active allylic alcohol with lower enantiopurity (79.2% ee) by enrichment of enantiopurity. A general method for the determination of the enantiomeric excesses of (E)-allylsilanes is also described in detail.
- Suginome, Michinori,Iwanami, Taisuke,Ohmori, Yutaka,Matsumoto, Akira,Ito, Yoshihiko
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p. 2954 - 2965
(2007/10/03)
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- Nitrous oxide oxidation catalyzed by ruthenium porphyrin complex
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Dinitrogen oxide was employed as a clean oxidant for various oxidations in the presence of a catalytic amount of dioxoruthenium tetramesitylporphyrin complex (Ru(tmp)(O)2). A variety of olefins, secondary alcohols, and benzyl alcohols were smoothly oxidized to the corresponding epoxides, ketones, and aldehydes in high yields. In the oxidation of 9,10-dihydroanthracene derivatives, the competitive reactions affording anthraquinones and anthracenes could be regulated by the reaction conditions. At a high temperature (200°C), anthraquinones were selectively produced, while the anthracenes were selectively produced by the addition of sulfuric acid.
- Tanaka, Hirotaka,Hashimoto, Kentaro,Suzuki, Kyosuke,Kitaichi, Yasunori,Sato, Mitsuo,Ikeno, Taketo,Yamada, Tohru
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p. 1905 - 1914
(2007/10/03)
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- Tandem cross-metathesis/hydrogenation/cyclization reactions by using compatible catalysts
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(Matrix presented) A one-pot tandem cross-metathesis/hydrogenation/cyclization procedure was achieved at room temperature, under 1 atm of hydrogen, in the presence of a ruthenium catalyst and PtO2 showing the compatibility of the two catalysts. This tandem reaction allows the synthesis of substituted lactones and lactols from acrylic acid and acrolein, respectively, in the presence of unsaturated alcohols.
- Cossy, Janine,Bargiggia, Frederic,BouzBouz, Samir
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p. 459 - 462
(2007/10/03)
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- Palladium-catalyzed reduction of ketones with nBu2SnH2
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Whereas the Pd(PPh3)4-catalyzed reduction of ketones with nBu3SnH does not proceed at all, the use of nBu2SnH2, instead of nBu3SnH, leads to the efficient reduction of a variety of ketones in the presence of a catalytic amount of Pd(PPh3)4 under mild conditions, providing the corresponding alcohols in good yields. The stereoselectivity in the reduction of cyclic ketones is also investigated by using this Pd(PPh3)4/nBu2SnH2 reduction system.
- Kamiya, Ikuyo,Ogawa, Akiya
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p. 1701 - 1703
(2007/10/03)
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- Synthesis of highly enantio-enriched allylsilanes via palladium-catalyzed intramolecular bis-silylation. Determination of the enantiomeric excesses through regio- and stereoselective hydroboration with 9-BBN
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Highly enantio-enriched (E)-allylsilanes, were synthesized by palladium-catalyzed intramolecular bis-silylation of chiral allyl alcohols and subsequent Peterson-type elimination with organolithium reagents, The enantiomeric excesses of the allylsilanes were determined after hydroboration with 9-BBN followed by oxidation, revealing remarkably high stereospecificity for the present synthesis.
- Suginome, Michinori,Iwanami, Taisuke,Matsumoto, Akira,Yoshihiko, Ito
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p. 859 - 862
(2007/10/03)
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- Decane autoxidation: Precursors of gamma lactones and other minor products
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Autoxidation of decane produces the following minor products in decreasing yields, viz. 2,5-, 3,6- and 4,7-decanediones and diols. Addition of 3-decanone to a decane autoxidation enhances the production of octanal, heptanal, octanoic and heptanoic acids. 3-Decanol initially inhibits the autoxidation reaction prior to being oxidized to 3-decanone. γ-Octanoic and γ-heptanoic lactone formation in the autoxidation of decane is promoted by the addition of 3- and 4-decyl hydroperoxides, respectively. These lactones are formed when tert-butoxy radicals react with 3,6- and 4,7-decane diols in the presence of oxygen. The nature of the intermediates in the formation of the minor products and the inhibition by alcohols are discussed.
- Goosen, Andre,Kindermans, Sybrandus
-
-
- Stereospecific internal almylation of terminal γ,δ-epoxy acrylates
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The alkylation of ethyl (S)- and (R)-4,5-epoxy-2-pentenoates (11) and (12), chiral terminal γ,δ-epoxy acrylates prepared from D-mannitol, by trialkylaluminum in the presence of water occurs rcgioselectively at the γ position, i.e., at the internal position, to yield a sole product respectively with net inversion of configuration. The method provides useful chiral synthons for natural product synthesis.
- Miyazawa, Masahiro,Ishibashi, Naoki,Ohnuma, Satoshi,Miyashita, Masaaki
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p. 3419 - 3422
(2007/10/03)
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- Chiral N,N-Dialkylnorephedrines as Catalysts of the Highly Enantioselective Addition of Dialkylzincs to Aliphatic and Aromatic Aldehydes. The Asymmetric Synthesis of Secondary Aliphatic and Aromatic Alcohols of High Optical Purity
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The chiral N,N-dialkylnorephedrine-catalyzed addition of dialkylzincs to aliphatic and aromatic aldehydes afforded secondary alcohols of high optical purity (to > 95percent ee).Among the N,N-di(primary alkyl)norephedrines, N,N-di-n-butylnorephedrine (DBNE, 3d) was found to be the most effective catalyst. 1-Phenyl-2-(1-pyrrolidinyl)propan-1-ol (3i) and N,N-diallylnorephedrine (3j) were also highly effective catalysts.The method described provides optically active secondary aliphatic alcohols of high optical purity which cannot be prepared by conventional methods.
- Soai, Kenso,Yokoyama, Shuji,Hayasaka, Tomoiki
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p. 4264 - 4268
(2007/10/02)
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- Shape Selective Alkane Hydroxylation by Metalloporphyrin Catalysts
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A series of manganese and iron porphyrins with sterically protected pockets are shown to be shape selective alkane hydroxylation catalysts.With iodosobenzene as oxidant, good regioselectivity is observed for hydroxylation of alkanes at the least hindered methyl group by using the very sterically hindered (5,10,15,20-tetrakis(2',4',6'-triphenylphenyl)porphyrinato)manganese(III) acetate (MnTTPPP(OAc)) as catalyst; The moderately hindered (5,10,15,20-tetrakis(2',4',6'-trimethoxyphenyl)porphyrinato)manganese(III) acetate shows little selectivity toward terminal CH3 hydroxylation but does show enhancement for the adjacent, ω - 1, CH2 site.Primary selectivity is dependent on the size and shape of the alkane substrate, with more bulky substituents giving greater primary selectivity.Substituting pentafluoroiodosobenzene or m-chloroperbenzoic acid as oxidants yields similar selectivity, thus conclusively demonstrating metal based oxidation via a common intermediate for these three systems.In contrast, tert-butyl hydroperoxide or 2,2,2-trifluoroethanol solubilized pentafluoroiodosobenzene show no primary carbon selectivity, and reaction product ratios are independent of the metalloporphyrin catalyst; this demonstrates that the site of oxidation with these oxidants is not metal based.The iron porphyrin derivatives also show good primary selectivity, although to a lesser degree than with the Mn derivatives, proving that these oxidations too are metal based.The regioselectivities for alkane hydroxilation shown by TTPPP derivatives are comparable to or better than those found for some isozymes of cytochrome P-450 which are responsible for primary alcohol biosynthesis from steroids, fatty acids, and alkanes.
- Cook, Bruce R.,Reinert, Thomas J.,Suslick, Kenneth S.
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p. 7281 - 7286
(2007/10/02)
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- OXIDATION OF BENZYL ETHER TO BENZOATE BY OZONE
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Ozoniation of benzyl ethers at low temperatures in acetone or methanol solvent smoothly gave the corresponding benzoates in good yields.
- Hirama, Masahiro,Shimizu, Mitsuaki
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p. 781 - 786
(2007/10/02)
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- Cp2TiCl2-CATALYZED GRIGNARD REACTIONS. 3. REACTIONS WITH ESTERS: EFFICIENT METHODOLOGY FOR THE SYNTHESIS OF SECONDARY ALCOHOLS AND FOR THE REDUCTION OF ESTERS TO PRIMARY ALCOHOLS
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Cp2TiCl2-catalyzed Grignard reactions with esters provide general methodology for preparation of secondary alcohols or for reduction of esters to the corresponding primary alcohols.
- Sato, Fumie,Jinbo, Takamasa,Sato, Masao
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p. 2175 - 2178
(2007/10/02)
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