Showing papers on "Enone published in 2017"
TL;DR: The palladium-catalyzed asymmetric synthesis of enone-based atropisomers from 2-iodo-3-methylcyclohex-2-enones and aryl boronic acid is reported and BoPhoz-type phosphine-aminophosphine ligands showed superior enantioselectivity over other ligands.
Abstract: The palladium-catalyzed asymmetric synthesis of enone-based atropisomers from 2-iodo-3-methylcyclohex-2-enones and aryl boronic acid is reported. BoPhoz-type phosphine–aminophosphine ligands showed superior enantioselectivity over other ligands. These cyclohexenone-based atropisomers are useful compounds for further elaboration. The divergent synthesis of biaryl atropisomers with different ortho substituents was demonstrated.
76 citations
TL;DR: The authors show the versatile copper-catalyzed successive dehydrogenation of a variety of organic substrates affording highly conjugated unsaturated products.
Abstract: In organic molecules, the reactivity at the carbon atom next to the functional group is dramatically different from that at other carbon atoms. Herein, we report that a versatile copper-catalyzed method enables successive dehydrogenation or dehydrogenation of ketones, aldehydes, alcohols, α,β-unsaturated diesters, and N-heterocycles to furnish stereodefined conjugated dienecarbonyls, polyenecarbonyls, and nitrogen-containing heteroarenes. On the basis of mechanistic studies, the copper-catalyzed successive dehydrogenation process proceeds via the initial α,β-desaturation followed by further dehydrogenative desaturation of the resultant enone intermediate, demonstrating that the reactivity at α-carbon is transferred through carbon-carbon double bond or longer π-system to the carbon atoms at the positions γ, e, and η to carbonyl groups. The dehydrogenative desaturation-relay is ascribed to the formation of an unusual radical intermediate stabilized by 5- or 7,- or 9-center π-systems. The discovery of successive dehydrogenation may open the door to functionalizations of the positions distant from functional groups in organic molecules.
59 citations
TL;DR: The telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts.
Abstract: The telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences.
53 citations
TL;DR: Mechanistic studies revealed that the rare-earth metal-catalyzed polymerizations were initiated by new FLP-type 1,4-additions rather than traditional and ubiquitous covalent RE-E (E=H, C, N, etc.) bond insertion or single-electron transfer.
Abstract: Three rare-earth aryloxide ion pairs {[L1REOAr]+ /[B(C6 F5 )4 ]- ; L1=CH3 C(2,6-iPr2 C6 H3 N)CHC(CH3 )(NCH2 CH2 PPh2 ); RE=Sc, Y, Lu; Ar=2,6-tBu2 C6 H3 } were reported that feature rare-earth/phosphorus (RE/P) combinations exhibiting frustrated Lewis pair (FLP)-like 1,4-addition reactions towards conjugated carbonyl substrates (e.g., enone, ynone, and acrylic substrates). Furthermore, these RE/P complexes were found to be effective catalysts for the polymerization of conjugated polar alkene monomers. Mechanistic studies revealed that the rare-earth metal-catalyzed polymerizations were initiated by new FLP-type 1,4-additions rather than traditional and ubiquitous covalent RE-E (E=H, C, N, etc.) bond insertion or single-electron transfer.
52 citations
TL;DR: It is shown that the enone functional group, upon photoexcitation, provides a solution for site-selective photochemical fluorination of complex substrates that should be relevant to drug discovery, where fluorine plays a prominent role.
Abstract: In the realm of aliphatic fluorination, the problem of reactivity has been very successfully addressed in recent years. In contrast, the associated problem of selectivity, that is, directing fluorination to specific sites in complex molecules, remains a great, fundamental challenge. In this report, we show that the enone functional group, upon photoexcitation, provides a solution. Based solely on orientation of the oxygen atom, site-selective photochemical fluorination is achieved on steroids and bioactive polycycles with up to 65 different sp3 C—H bonds. We have also found that γ-, β-, homoallylic, and allylic fluorination are all possible and predictable through the theoretical modes reported herein. Lastly, we present a preliminary mechanistic hypothesis characterized by intramolecular hydrogen atom transfer, radical fluorination, and ultimate restoration of the enone. In all, these results provide a leap forward in the design of selective fluorination of complex substrates that should be relevant to d...
50 citations
TL;DR: It is found that installation of a nucleophilic functional group at the γ-position of an enone greatly accelerates the rate of the diastereoselective intermolecular RC reaction, enabling an efficient and selective formation of the dimeric intermediate which was further transformed to (-)-flueggenine C.
Abstract: The first total synthesis of dimeric securinega alkaloid (−)-flueggenine C is completed via an accelerated intermolecular Rauhut–Currier (RC) reaction. Despite the numerous reports on the total synthesis of monomeric securinegas, the synthesis of dimeric securinegas whose monomeric units are connected by a putative enzymatic RC reaction has not been reported to date. We have found that installation of a nucleophilic functional group at the γ-position of an enone greatly accelerates the rate of the diastereoselective intermolecular RC reaction. This discovery enabled an efficient and selective formation of the dimeric intermediate which was further transformed to (−)-flueggenine C.
40 citations
TL;DR: A novel and efficient synthesis of 3-acylpyridines and pyridine-3-carboxylates through the oxidative one-pot sequential reactions of inactivated saturated ketones with electron-deficient enamines is presented.
Abstract: In this paper, a novel and efficient synthesis of 3-acylpyridines and pyridine-3-carboxylates through the oxidative one-pot sequential reactions of inactivated saturated ketones with electron-deficient enamines is presented. Mechanistically, the formation of the title compounds involves the in situ formation of an enone intermediate through an oxidative dehydrogenation of the saturated ketone substrate, followed by its [3+3] annulation with β-enaminone or β-enaminoester via a cascade process, including Michael addition, aldol type condensation, and oxidative aromatization.
37 citations
TL;DR: The first enantioselective total synthesis of (-)-cycloclavine was accomplished in 8 steps and 7.1 % overall yield, and key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh2, and the enone 1,2-addition of a new TEMPO carbamate methyl carbanion.
Abstract: The first enantioselective total synthesis of (−)-cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh2(S-TBPTTL)4, and the enone 1,2-addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain-promoted Diels–Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99 % ee after crystallization. The synthesis of (−)-1 was completed by a late-stage intramolecular Diels–Alder furan (IMDAF) cycloaddition to install the indole.
37 citations
TL;DR: In this article, the use of cooperative catalysis using Lewis acids and chiral Bronsted acids to control the chirality of a tertiary α-carbon in the products of a Nazarov cyclization of enones is presented.
Abstract: Enantioselective control of the chirality of a tertiary α-carbon in the products of a Nazarov cyclization of enones is challenging because the reaction involves an enantioselective proton transfer process. We herein report the use of cooperative catalysis using Lewis acids and chiral Bronsted acids to control the stereochemistry of the tertiary α-carbon in the products of this reaction. Specifically, with ZnCl2 and a chiral spiro phosphoric acid as catalysts, we realized the first enantioselective construction of cyclopenta[b]indoles with chiral tertiary α-carbons via Nazarov cyclization of indole enone substrates with only one coordinating site. Mechanistic studies revealed that the chiral spiro phosphoric acid acts as a multifunctional catalyst: it co-catalyzes the cyclization of the dienone and enantioselectively catalyzes a proton transfer reaction of the enol intermediate. This new strategy of enantioselective control by means of cooperative catalysis may show utility for other challenging asymmetric cyclization reactions.
36 citations
TL;DR: A Ti(Oi-Pr)4-promoted photoenolization/Diels–Alder (PEDA) reaction to construct hydroanthracenol and related polycyclic rings bearing all-carbon quaternary centers and the total synthesis of oncocalyxone B was successfully achieved using this PEDA approach.
Abstract: Stereoselective construction of polycyclic rings with all-carbon quaternary centers, and vicinal all-carbon quaternary stereocenters, remains a significant challenge in organic synthesis. These structures can be found in a wide range of polycyclic natural products and drug molecules. Here we report a Ti(Oi-Pr)4-promoted photoenolization/Diels–Alder (PEDA) reaction to construct hydroanthracenol and related polycyclic rings bearing all-carbon quaternary centers. This photolysis proceeds under mild conditions and generates a variety of photo-cycloaddition products in good reaction efficiency and stereoselectivity (48 examples), and has been successfully used in the construction of core skeleton of oncocalyxones, tetracycline and pleurotin. It also provides a reliable method for the late-stage modification of natural products bearing enone groups, such as steroids. The total synthesis of oncocalyxone B was successfully achieved using this PEDA approach. Anthracenols with multiple chiral centres are common motifs in natural products. Here, the authors show a highly stereoselective photoenolization/Diels–Alder methodology involving a key Lewis acid reagent enabling the efficient construction of a family of anthracenol derivatives with quaternary centers.
36 citations
TL;DR: Dithiane‐protected enones (enone dithianes) were found to undergo an intramolecular [2+2] photocycloaddition under visible‐light irradiation in the presence of a Brønsted acid, and cyclobutanes were obtained in very good yields.
Abstract: 1,3-Dithiane-protected enones (enone dithianes) were found to undergo an intramolecular [2+2] photocycloaddition under visible-light irradiation (λ=405 nm) in the presence of a Bronsted acid (7.5–10 mol %). Key to the success of the reaction is presumably the formation of colored thionium ions, which are intermediates of the catalytic cycle. Cyclobutanes were thus obtained in very good yields (78–90 %). It is also shown that the dithiane moiety can be reductively or oxidatively removed without affecting the photochemically constructed ring skeleton.
TL;DR: This is the first example in which the biologically and pharmaceutically important yet otherwise difficult-to-obtain 4-acylpyrazole derivatives are directly prepared from saturated ketones and hydrazones featured with multiple aliphatic C-H bond functionalization and C-C bond cleavage and reorganization.
Abstract: In this paper, an efficient and convenient one-pot synthesis of diversely substituted 4-acylpyrazole derivatives via copper-catalyzed one-pot cascade reactions of saturated ketones with hydrazones is reported. Mechanistically, the formation of the title compounds involves the in situ formation of an enone intermediate through the dehydrogenation of a saturated ketone and the [2 + 3] cyclization of the enone with hydrazone followed by an aromatization-driven C–C bond cleavage and reorganization. To our knowledge, this is the first example in which the biologically and pharmaceutically important yet otherwise difficult-to-obtain 4-acylpyrazole derivatives are directly prepared from saturated ketones and hydrazones featured with multiple aliphatic C–H bond functionalization and C–C bond cleavage and reorganization. Compared with literature methods, this novel process has advantages such as simple and economical starting materials, a sustainable oxidant, excellent regioselectivity, and good efficiency.
TL;DR: This synthetic work allowed us to determine the axial chirality of the 2,2'-biaryl C-C bond and the absolute configuration of the ascherxanthone A, which should facilitate the preparation of derivatives and structurally related natural products for medicinal studies.
TL;DR: In this paper, the influence of metal-organic frameworks (MOFs) as additives is described for the reaction of n-alkyl aldehydes in the presence of methylvinylketone and triphenylphosphine.
Abstract: The influence of metal–organic frameworks (MOFs) as additives is herein described for the reaction of n-alkyl aldehydes in the presence of methylvinylketone and triphenylphosphine. In the absence of a MOF, the expected Morita–Baylis–Hillman product, a β-hydroxy enone, is observed. In the presence of MOFs with UMCM-1 and MOF-5 topologies, the reaction is selective to Aldol-Tishchenko products, the 1 and 3 n-alkylesters of 2-alkyl-1,3-diols, which is unprecedented in organocatalysis. The (3-oxo-2-butenyl)triphenylphosphonium zwitterion, a commonly known nucleophile, is identified as the catalytic active species. This zwitterion favors nucleophilic character in solution, whereas once confined within the framework, it becomes an electrophile yielding Aldol-Tishchenko selectivity. Computational investigations reveal a structural change in the phosphonium moiety induced by the steric confinement of the framework that makes it accessible and an electrophile.
TL;DR: A unified dynamic kinetic spiroketalization/enantioselective oxa-Michael addition cascade of an aromatic ketone tethered to an alkoxyboronate and an enone moiety has been developed using cinchona alkaloid based amino-thiourea/squaramide organocatalysts to provide isobenzofuran-based benzannulated spirokenals with high diastereoselectivities and excellent enantioselectedivities.
Abstract: A unified dynamic kinetic spiroketalization/enantioselective oxa-Michael addition cascade of an aromatic ketone tethered to an alkoxyboronate and an enone moiety has been developed using cinchona alkaloid based amino-thiourea/squaramide organocatalysts to provide isobenzofuran-based benzannulated spiroketals with high diastereoselectivities and excellent enantioselectivities. Further, a dynamic kinetic peroxy-hemiacetalization/dynamic kinetic spiroketalization/enantioselective oxa-Michael addition cascade of the above substrates provides the corresponding exo-peroxy-benzannulated spiroketals with outstanding enantio- and diastereoselectivities.
TL;DR: By the use of the gem-diester functional handle present in the adducts, local desymmetrization via diastereotopic group discrimination was demonstrated, and a polyfunctionalized lactam with three contiguous stereocenters was synthesized.
TL;DR: In this paper, a novel asymmetric synthesis of all-carbon quaternary stereogenic centres is developed by the connection of three prochiral or achiral components (conjugated enones, organometallic compounds and vinyl esters) at the C-1 position of enones.
TL;DR: In this article, a new synthesis of both enantiomers of naturally occurring febrifugine (1) and its analogue halofuginone (3) is reported, relying on an enzymatic kinetic resolution (EKR)-cross metathesis (CM) sequence, performed on allylic alcohol 8.
TL;DR: A double-activation strategy for α'-alkylidene cyclic enone substrates that uses a chiral primary amine and 2-mercaptobenzoic acid to promote regio- and chemoselective addition to generate the complex interrupted iminium ion species.
Abstract: Cooperative catalysis has contributed greatly to the progress of asymmetric synthesis. However, double-activation catalysis has been less explored, especially for covalently tethered species. Here, we present a double-activation strategy for α'-alkylidene cyclic enone substrates that uses a chiral primary amine and 2-mercaptobenzoic acid to promote regio- and chemoselective addition to generate the complex interrupted iminium ion species. Significantly enhanced reactivity and enantioselectivity were observed for β-regioselective Michael addition and Friedel-Crafts alkylation with malononitriles and indoles, respectively, which produced a spectrum of chiral cyclic adducts with an exo-alkylidene group. Moreover, a HRMS study detected a few key covalently tethered intermediates among the substrates and catalysts, which helped elucidate the catalytic mechanism.
TL;DR: The observed experimental results further support the proposed mechanism for the ketonic decarboxylation via the β-keto acid intermediate, and are revisited and discussed herein.
Abstract: For the reaction mechanism of the ketonic decarboxylation of two carboxylic acids, a β-keto acid is favored as key intermediate in many experimental and theoretical studies. Hydrogen atoms in the α-position are an indispensable requirement for the substrates to react by following this mechanism. However, isolated observations with tertiary carboxylic acids are not consistent with it and these are revisited and discussed herein. The experimental results obtained with pivalic acid indicate that the ketonic decarboxylation does not occur with this substrate. Instead, it is consumed in alternative reactions such as disintegration into isobutene, carbon monoxide, and water (retro-Koch reaction). In addition, the carboxylic acid is isomerized or loses carbon atoms, which converts the tertiary carboxylic acid into carboxylic acids bearing α-proton atoms. Hence, the latter are suitable to react through the β-keto acid pathway. A second substrate, 2,2,5,5-tetramethyladipic acid, reacted by following the same retro-Koch pathway. The primary product was the monocarboxylic acid 2,2,5-trimethyl-4-hexenoic acid (and its double bond isomer), which might be further transformed into a cyclic enone or a lactone. The ketonic decarboxylation product, 2,2,5,5-tetramethylcyclopentanone was observed in traces (<0.2 % yield). Therefore, it can be concluded that the observed experimental results further support the proposed mechanism for the ketonic decarboxylation via the β-keto acid intermediate.
TL;DR: An efficient method for direct formation of epoxide groups from carbon(sp2)-carbon(sp3) single bonds of β-keto esters is developed; the reaction is mediated by the water-soluble hypervalent iodine(V) reagent AIBX.
Abstract: We have developed an efficient method for direct formation of epoxide groups from carbon(sp2)–carbon(sp3) single bonds of β-keto esters; the reaction is mediated by the water-soluble hypervalent iodine(V) reagent AIBX (5-trimethylammonio-1,3-dioxo-1,3-dihydro-1λ5-benzo[d][1,2]iodoxol-1-ol anion) On the basis of the results of density functional theory calculations and experimental studies, we propose that the reaction proceeds by a two-stage mechanism involving dehydrogenation of the β-keto ester substrates and epoxidation of the resulting enone intermediates The rate-limiting step is abstraction of the β′-C–H (calculated free energy of activation, 245 kcal/mol)
TL;DR: The highly enantioselective alkylation of α-CF3 enolates, generated from triketopiperazines, has been accomplished through use of a bifunctional thiourea organocatalyst to facilitate 1,4-addition to varied enone acceptors.
Abstract: The highly enantioselective alkylation of α-CF3 enolates, generated from triketopiperazines, has been accomplished through use of a bifunctional thiourea organocatalyst to facilitate 1,4-addition to varied enone acceptors. On treatment with appropriate nitrogen nucleophiles, the chiral triketopiperazine products undergo a metamorphosis, to provide novel fused heterocyclic lactams such as extended pyrazolopyrimidines.
TL;DR: In this article, a vapor phase intramolecular aldol condensation of 2,5-hexanedione to produce 3-methylcyclopent-2-enone was performed over several ZrO 2 -supported alkali and alkali earth metal oxides.
TL;DR: This dual catalysis protocol was successfully applied to the reaction of a variety of aliphatic- and aromatic-substituted enone substrates.
Abstract: Double asymmetric hydrogenation of linear β,β-disubstituted α,β-unsaturated ketones catalyzed by the DM-SEGPHOS/DMAPEN/RuII complex with t-C4H9OK afforded the γ-substituted secondary alcohols in high diastereo- and enantioselectivities. Some mechanistic experiments suggested that two different reactive species, type (I) and (II), were reversibly formed in this catalytic system: Type (I) with the diamine ligand DMAPEN enantioselectively hydrogenated the enones into the chiral allylic alcohols, and type (II) without the diamine ligand diastereoselectively hydrogenated the allylic alcohols into the γ-substituted secondary alcohols. This dual catalysis protocol was successfully applied to the reaction of a variety of aliphatic- and aromatic-substituted enone substrates.
TL;DR: In this paper, a transition-metal-free strategy for the synthesis of pyrrolo[1,2-a]pyrazines with enone substituents has been developed.
Abstract: A concise transition-metal-free strategy for the synthesis of pyrrolo[1,2-a]pyrazines with enone substituents has been developed. It includes the following key steps: (a) cross-coupling of pyrroles with acyl(bromo)acetylenes in solid alumina at room temperature to give 2-(acylethynyl)pyrroles; (b) addition of propargylamine to the above acetylenes to form the corresponding N-propargylenaminones; and (c) chemo- and stereoselective base-catalyzed (Cs2CO3/DMSO) intramolecular cyclization of the synthesized propargylic derivatives to form (acylmethylidene)pyrrolo[1,2-a]pyrazines of Z-configuration.
TL;DR: In this paper, a direct access to 3,5-disubstituted isoxazoles has been accomplished through an intramolecular oxidative coupling reaction of enone oximes using a catalytic quantity of Cu(OAc)2.
Abstract: A direct access to 3,5-disubstituted isoxazoles has been accomplished through an intramolecular oxidative coupling reaction of enone oximes using a catalytic quantity of Cu(OAc)2. This method features an inexpensive metal catalyst, molecular oxygen as a green oxidant, good functional group tolerance and readily available starting materials. This attractive method for the synthesis of isoxazole derivatives is of great significance due to the product's versatile reactivity for further transformations.
TL;DR: In this article, a highly stereoselective total synthesis of Amaryllidaceae alkaloid starting from α-d -galactopyranoside has been described and the salient features of this total synthesis are Ferrier carbocyclization reaction for synthesis of ring A and Suzuki Miyaura coupling of chiral α-iodo enone fragment with aromatic boronic acid followed by modified Bischler-Napieralski cyclization reaction to form the lactam ring.
TL;DR: The emerging picture suggests that the triterpenoid scaffold sharply decreases the reactivity of the enone system by steric encumbrance and that only strongly electrophilic and sterically undemanding substituents such as a cyanide or a carboxylate group can re-establish Michael reactivity, albeit in a transient way for the cyanide group.
Abstract: Bardoxolone methyl (1) is the quintessential member of triterpenoid cyanoacrylates, an emerging class of bioactive compounds capable of transient covalent binding to thiols. The mechanistic basis for this unusual “pulsed reactivity” profile and the mode of its biological translation are unknown. To provide clues on these issues, a series of Δ1-dehydrooleanolates bearing an electron-withdrawing group at C-2 (7a–m) were prepared from oleanolic acid (3a) and comparatively investigated in terms of reactivity with thiols and bioactivity against a series of electrophile-sensitive transcription factors (Nrf2, NF-κB, STAT3). The emerging picture suggests that the triterpenoid scaffold sharply decreases the reactivity of the enone system by steric encumbrance and that only strongly electrophilic and sterically undemanding substituents such as a cyanide or a carboxylate group can re-establish Michael reactivity, albeit in a transient way for the cyanide group. In general, a substantial dissection between the thiol-...
TL;DR: The total synthesis of orientalol F has been achieved starting from 1,4-dioxaspirodecan-8-one in 13 steps as mentioned in this paper, and the key steps in this synthesis feature: (1) gold-catalyzed tandem cycloisomerization of alkynediol 10 for the formation of its seven-membered oxa-bridged bicyclic skeleton, (2) visible-light-promoted organocatalytic aerobic oxidation of silyl enol ether 16 to enone 17, (3) Barbier-type
Abstract: The total synthesis of orientalol F has been achieved starting from 1,4-dioxaspirodecan-8-one 11 in 13 steps. The key steps in this synthesis feature: (1) gold-catalyzed tandem cycloisomerization of alkynediol 10 for the formation of its seven-membered oxa-bridged bicyclic skeleton 9 of orientalol F, (2) visible-light-promoted organocatalytic aerobic oxidation of silyl enol ether 16 to enone 17, (3) Barbier-type butenylation for the diastereoselective synthesis of allylic alcohol 18 from enone 17, and (4) substrate-controlled Pd-catalyzed hydrogenation of 20 for the stereoselective installation of the C1 stereogenic center of 8.
TL;DR: A novel enone reductase from Sporidiobolus salmonicolor TPU 2001 (SsERD) is discovered and expressed the gene in Escherichia coli and catalyzed the reduction of carbon–carbon double bond of large monocyclic enones.
Abstract: We discovered a novel enone reductase from Sporidiobolus salmonicolor TPU 2001 (SsERD) and successfully expressed it in Escherichia coli. The enzyme catalyzed the reduction of (E)-3-methylcyclopentadec-2-en-1-one (E-2), cyclopentadec-2-en-1-one (3), and cyclododec-2-en-1-one (4) to (S)-muscone (S-1), cyclopentadecan-1-one (5), and cyclododecan-1-one (6), respectively. The apparent Km and Vmax values for E-2 were estimated to be 4.9 ± 0.4 μM and 100 ± 1.4 nmol min-1 mg-1, respectively. The enzyme is specific to NADPH, and cysteine residue strongly affects the enzyme activity. The enzyme exhibited the highest activity at pH 8.0 and high stability in the pH range from 4.5 to 11.0. Using 10 mU of the enzyme, S-1 was synthesized from 0.1 mM E-2 with 94.8% yield and 100% enantiomeric excess by incubation at pH 7.0 and 30 °C for 60 min. We further successfully constructed enone reductase with high specific activity by mutation of SsERD. The Y67A variant from SsERD exhibited 4.5 times higher specific activity and 3 times higher catalytic efficiency toward E-2. This is the first report of the enzyme catalyzing reduction of carbon-carbon double bond of large monocyclic enones.