6909-25-7Relevant academic research and scientific papers
Total Synthesis of (?)-Rotundone and (?)-epi-Rotundone from Monoterpene Precursors
Rüthi, Fabian,Schr?der, Fridtjof
, (2020/10/30)
The first total synthesis of (?)-rotundone has been accomplished from (+)-(R)-limonene and therefore for the first time from an unrelated monoterpene instead of modifying structurally closely related sesquiterpene precursors such as α-guaiene. Challenges such as intermediates with stereocenters prone to epimerization by enolization were overcome by designing a β-methyl-keto route starting from (+)-(R)-limonene which finally gave (?)-rotundone by Nazarov cyclization of a precursor 13a. Diastereomer (?)-epi-rotundone was separated from (?)-rotundone chromatographically. An alternative route from rac-citronellal provided a diastereomer mixture of racemic Nazarov precursor 13 through a TRIP-catalyzed intramolecular aldolization, thus indicating that the Nazarov cyclization precursor 13a is in principle accessible from (?)-(S)-citronellal. The 11-step synthesis from (+)-(R)-limonene with ca. 1 % overall yield confirmed the absolute configuration of (?)-rotundone and provided samples of good olfactory quality.
Photocontrolled Cobalt Catalysis for Selective Hydroboration of α,β-Unsaturated Ketones
Beltran, Frédéric,Bergamaschi, Enrico,Funes-Ardoiz, Ignacio,Teskey, Christopher J.
supporting information, p. 21176 - 21182 (2020/09/17)
Selectivity between 1,2 and 1,4 addition of a nucleophile to an α,β-unsaturated carbonyl compound has classically been modified by the addition of stoichiometric additives to the substrate or reagent to increase their “hard” or “soft” character. Here, we demonstrate a conceptually distinct approach that instead relies on controlling the coordination sphere of a catalyst with visible light. In this way, we bias the reaction down two divergent pathways, giving contrasting products in the catalytic hydroboration of α,β-unsaturated ketones. This includes direct access to previously elusive cyclic enolborates, via 1,4-selective hydroboration, providing a straightforward and stereoselective route to rare syn-aldol products in one-pot. DFT calculations and mechanistic experiments confirm two different mechanisms are operative, underpinning this unusual photocontrolled selectivity switch.
Synthesis and Biochemical Evaluation of Nicotinamide Derivatives as NADH Analogue Coenzymes in Ene Reductase
Falcone, Natashya,She, Zhe,Syed, Jebreil,Lough, Alan,Kraatz, Heinz-Bernhard
, p. 838 - 845 (2019/02/07)
Nicotinamide and pyridine-containing conjugates have attracted a lot of attention in research as they have found use in a wide range of applications including as redox flow batteries and calcium channel blockers, in biocatalysis, and in metabolism. The interesting redox character of the compounds’ pyridine/dihydropyridine system allows them to possess very similar characteristics to the natural chiral redox agents NAD+/NADH, even mimicking their functions. There has been considerable interest in designing and synthesizing NAD+/NADH mimetics with similar redox properties. In this research, three nicotinamide conjugates were designed, synthesized, and characterized. Molecular structures obtained through X-ray crystallography were obtained for two of the conjugates, thereby providing more detail on the bonding and structure of the compounds. The compounds were then further evaluated for biochemical properties, and it was found that one of the conjugates possessed similar functions and characteristics to the natural NADH. This compound was evaluated in the active enzyme, enoate reductase; like NADH, it was shown to help reduce the C=C double bond of three substrates and even outperformed the natural coenzyme. Kinetic data are reported.
C3 and C6 Modification-Specific OYE Biotransformations of Synthetic Carvones and Sequential BVMO Chemoenzymatic Synthesis of Chiral Caprolactones
Issa, Issa S.,Toogood, Helen S.,Johannissen, Linus O.,Raftery, James,Scrutton, Nigel S.,Gardiner, John M.
supporting information, p. 2983 - 2988 (2019/01/24)
The scope for biocatalytic modification of non-native carvone derivatives for speciality intermediates has hitherto been limited. Additionally, caprolactones are important feedstocks with diverse applications in the polymer industry and new non-native terpenone-derived biocatalytic caprolactone syntheses are thus of potential value for industrial biocatalytic materials applications. Biocatalytic reduction of synthetic analogues of R-(?)-carvone with additional substituents at C3 or C6, or both C3 and C6, using three types of OYEs (OYE2, PETNR and OYE3) shows significant impact of both regio-substitution and the substrate diastereomer. Bioreduction of (?)-carvone derivatives substituted with a Me and/or OH group at C6 is highly dependent on the diastereomer of the substrate. Derivatives bearing C6 substituents larger than methyl moieties are not substrates. Computer docking studies of PETNR with both (6S)-Me and (6R)-Me substituted (?)-carvone provides a model consistent with the outcomes of bioconversion. The products of bioreduction were efficiently biotransformed by the Baeyer–Villiger monooxygenase (BVase) CHMO_Phi1 to afford novel trisubstituted lactones with complete regioselectivity to provide a new biocatalytic entry to these chiral caprolactones. This provides both new non-native polymerization feedstock chemicals, but also with enhanced efficiency and selectivity over native (+)-dihydrocarvone Baeyer–Villigerase expansion. Optimum enzymatic reactions were scaled up to 60–100 mg, demonstrating the utility for preparative biocatalytic synthesis of both new synthetic scaffold-modified dihydrocarvones and efficient biocatalytic entry to new chiral caprolactones, which are potential single-isomer chiral polymer feedstocks.
Heteropoly acid catalysis for the isomerization of biomass-derived limonene oxide and kinetic separation of the trans-isomer in green solvents
Cotta, Rafaela F.,Martins, Rafael A.,Pereira, Matheus M.,da Silva Rocha, Kelly A.,Kozhevnikova, Elena F.,Kozhevnikov, Ivan V.,Gusevskaya, Elena V.
, (2019/08/02)
Terpenes are an abundant class of natural products, which is important for flavor and fragrance industry. Many acid catalyzed reactions used for upgrading terpenes still involve mineral acids as homogeneous catalysts and/or toxic solvents. Heteropoly acids represent a well-established eco-friendly alternative to conventional acid catalysts. As these reactions are usually performed in the liquid phase, solvents play a critical role for the process sustainability. In the present work, we developed a catalytic route to valuable fragrance ingredients, dihydrocarvone and carvenone, from limonene oxide by its isomerization using silica-supported tungstophosphoric acid as a heterogeneous catalyst and dialkylcarbonates as green solvents. The reaction pathway can be switched between dihydrocarvone and carvenone (obtained in 90% yield each) simply by changing the reaction temperature. In addition, we developed an efficient method for kinetic separation of trans-limonene oxide from commercial cis/trans-limonene oxide mixture and stereoselective synthesis of trans-dihydrocarvone.
Hydrogenation of Carbonyl Derivatives Catalysed by Manganese Complexes Bearing Bidentate Pyridinyl-Phosphine Ligands
Wei, Duo,Bruneau-Voisine, Antoine,Chauvin, Téo,Dorcet, Vincent,Roisnel, Thierry,Valyaev, Dmitry A.,Lugan, No?l,Sortais, Jean-Baptiste
supporting information, p. 676 - 681 (2017/12/26)
Manganese(I) catalysts incorporating readily available bidentate 2-aminopyridinyl-phosphine ligands achieve a high efficiency in the hydrogenation of carbonyl compounds, significantly better than parent ones based on more elaborated and expensive tridentate 2,6-(diaminopyridinyl)-diphosphine ligands. The reaction proceeds with low catalyst loading (0.5 mol%) under mild conditions (50 °C) with yields up to 96%. (Figure presented.).
Enantio- A nd regioselective: Ene-reductions using F420H2-dependent enzymes
Mathew, Sam,Trajkovic, Milos,Kumar, Hemant,Nguyen, Quoc-Thai,Fraaije, Marco W.
supporting information, p. 11208 - 11211 (2018/10/15)
In the past decade it has become clear that many microbes harbor enzymes that employ an unusual flavin cofactor, the F420 deazaflavin cofactor. Herein we show that F420-dependent reductases (FDRs) can successfully perform enantio-, regio- A nd chemoselective ene-reductions. For the first time, we have demonstrated that F420H2-driven reductases can be used as biocatalysts for the reduction of α,β-unsaturated ketones and aldehydes with good conversions (>99%) and excellent regioselectivities and enantiomeric excesses (>99% ee). Noteworthily, FDRs typically display an opposite enantioselectivity when compared to the well established FMN-dependent Old Yellow Enzymes (OYEs).
Investigating: Saccharomyces cerevisiae alkene reductase OYE 3 by substrate profiling, X-ray crystallography and computational methods
Powell, Robert W.,Buteler, M. Pilar,Lenka, Sunidhi,Crotti, Michele,Santangelo, Sara,Burg, Matthew J.,Bruner, Steven,Brenna, Elisabetta,Roitberg, Adrian E.,Stewart, Jon D.
, p. 5003 - 5016 (2018/10/17)
Saccharomyces cerevisiae OYE 3 shares 80% sequence identity with the well-studied Saccharomyces pastorianus OYE 1; however, wild-type OYE 3 shows different stereoselectivities toward some alkene substrates. Site-saturation mutagenesis of Trp 116 in OYE 3 followed by substrate profiling showed that the mutations had relatively little effect, opposite to that observed previously for OYE 1. The X-ray crystal structures of unliganded and phenol-bound OYE 3 were solved to 1.8 and 1.9 ? resolution, respectively. Both structures were nearly identical to that of OYE 1, with only a single amino acid difference in the active site region (Ser 296 versus Phe 296, part of loop 6). Despite their essentially identical static X-ray structures, molecular dynamics (MD) simulations revealed that loop 6 conformations differed significantly in solution between OYE 3 and OYE 1. In OYE 3, loop 6 remained nearly as open as observed in the crystal structure; by contrast, loop 6 closed over the active site of OYE 1 by ca. 4 ?. Loop closure likely generates a greater number of active site protein contacts for substrate bound to OYE 1 as compared to OYE 3. These differences provide an explanation for the differing stereoselectivities of OYE 3 and OYE 1, despite their nearly identical X-ray crystal structures.
Novel concurrent redox cascades of (R)- and (S)-carvones enables access to carvo-lactones with distinct regio- and enantioselectivity
Iqbal, Naseem,Stewart, Jon D.,Macheroux, Peter,Rudroff, Florian,Mihovilovic, Marko D.
, p. 7389 - 7394 (2018/11/23)
Within this study, we investigated a one-pot enzymatic redox cascade composed of different enoate reductases (5 EREDs from diverse bacterial origins) and various Baeyer-Villiger monooxygenases (4 BVMOs) with complementary regioselectivity that enabled access to six out of eight carvo-lactone stereoisomers starting from readily available natural carvones. Applicability of this two-step cascade was demonstrated by preparative scale experiments yielding up to 76% of the desired chiral carvolactone.
Stereodivergent Synthesis of Carveol and Dihydrocarveol through Ketoreductases/Ene-Reductases Catalyzed Asymmetric Reduction
Guo, Jiyang,Zhang, Rui,Ouyang, Jingping,Zhang, Feiting,Qin, Fengyu,Liu, Guigao,Zhang, Wenhe,Li, Hengyu,Ji, Xiaohong,Jia, Xian,Qin, Bin,You, Song
, p. 5496 - 5504 (2018/11/30)
Chiral carveol and dihydrocarveol are important additives in the flavor industry and building blocks in the synthesis of natural products. Despite the remarkable progress in asymmetric catalysis, convenient access to all possible stereoisomers of carveol and dihydrocarveol remains a challenge. Here, we present the stereodivergent synthesis of carveol and dihydrocarveol through ketoreductases/ene-reductases catalyzed asymmetric reduction. By directly asymmetric reduction of (R)- and (S)-carvone using ketoreductases, which have Prelog or anti-Prelog stereopreference, all four possible stereoisomers of carveol with medium to high diastereomeric excesses (up to >99 %) were first observed. Then four stereoisomers of dihydrocarvone were prepared through ene-reductases catalyzed diastereoselective synthesis. Asymmetric reduction of obtained dihydrocarvone isomers by ketoreductases further provide access to all eight stereoisomeric dihydrocarveol with up to 95 % de values. In addition, the absolute configurations of dihydrocarveol stereoisomers were determined by using modified Mosher's method.
