89-82-7Relevant articles and documents
Chemoenzymatic Synthesis of the Intermediates in the Peppermint Monoterpenoid Biosynthetic Pathway
Cheallaigh, Aisling Ní,Mansell, David J.,Toogood, Helen S.,Tait, Shirley,Lygidakis, Antonios,Scrutton, Nigel S.,Gardiner, John M.
, p. 1546 - 1552 (2018/08/04)
A chemoenzymatic approach providing access to all four intermediates in the peppermint biosynthetic pathway between limonene and menthone/isomenthone, including noncommercially available intermediates (-)-trans-isopiperitenol (2), (-)-isopiperitenone (3), and (+)-cis-isopulegone (4), is described. Oxidation of (+)-isopulegol (13) followed by enolate selenation and oxidative elimination steps provides (-)-isopiperitenone (3). A chemical reduction and separation route from (3) provides both native (-)-trans-isopiperitenol (2) and isomer (-)-cis-isopiperitenol (18), while enzymatic conjugate reduction of (-)-isopiperitenone (3) with IPR [(-)-isopiperitenone reductase)] provides (+)-cis-isopulegone (4). This undergoes facile base-mediated chemical epimerization to (+)-pulegone (5), which is subsequently shown to be a substrate for NtDBR (Nicotiana tabacum double-bond reductase) to afford (-)-menthone (7) and (+)-isomenthone (8).
Engineering the "missing Link" in Biosynthetic (-)-Menthol Production: Bacterial Isopulegone Isomerase
Currin, Andrew,Dunstan, Mark S.,Johannissen, Linus O.,Hollywood, Katherine A.,Vinaixa, Maria,Jervis, Adrian J.,Swainston, Neil,Rattray, Nicholas J. W.,Gardiner, John M.,Kell, Douglas B.,Takano, Eriko,Toogood, Helen S.,Scrutton, Nigel S.
, p. 2012 - 2020 (2018/03/13)
The realization of a synthetic biology approach to microbial (1R,2S,5R)-(-)-menthol (1) production relies on the identification of a gene encoding an isopulegone isomerase (IPGI), the only enzyme in the Mentha piperita biosynthetic pathway as yet unidentified. We demonstrate that Δ5-3-ketosteroid isomerase (KSI) from Pseudomonas putida can act as an IPGI, producing (R)-(+)-pulegone ((R)-2) from (+)-cis-isopulegone (3). Using a robotics-driven semirational design strategy, we identified a key KSI variant encoding four active site mutations, which confer a 4.3-fold increase in activity over the wild-type enzyme. This was assisted by the generation of crystal structures of four KSI variants, combined with molecular modeling of 3 binding to identify key active site residue targets. The KSI variant was demonstrated to function efficiently within cascade biocatalytic reactions with downstream Mentha enzymes pulegone reductase and (-)-menthone:(-)-menthol reductase to generate 1 from 3. This study introduces the use of a recombinant IPGI, engineered to function efficiently within a biosynthetic pathway for the production of 1 in microorganisms.
Pinpointing a Mechanistic Switch Between Ketoreduction and “Ene” Reduction in Short-Chain Dehydrogenases/Reductases
Lygidakis, Antonios,Karuppiah, Vijaykumar,Hoeven, Robin,Ní Cheallaigh, Aisling,Leys, David,Gardiner, John M.,Toogood, Helen S.,Scrutton, Nigel S.
supporting information, p. 9596 - 9600 (2016/08/10)
Three enzymes of the Mentha essential oil biosynthetic pathway are highly homologous, namely the ketoreductases (?)-menthone:(?)-menthol reductase and (?)-menthone:(+)-neomenthol reductase, and the “ene” reductase isopiperitenone reductase. We identified a rare catalytic residue substitution in the last two, and performed comparative crystal structure analyses and residue-swapping mutagenesis to investigate whether this determines the reaction outcome. The result was a complete loss of native activity and a switch between ene reduction and ketoreduction. This suggests the importance of a catalytic glutamate vs. tyrosine residue in determining the outcome of the reduction of α,β-unsaturated alkenes, due to the substrate occupying different binding conformations, and possibly also to the relative acidities of the two residues. This simple switch in mechanism by a single amino acid substitution could potentially generate a large number of de novo ene reductases.
Regioselective silver-mediated Kondakov-Darzens olefin acylation
Barczak, Nicholas T.,Jarvo, Elizabeth R.
, p. 12912 - 12916 (2011/12/04)
Enone construction: A silver-mediated olefin acylation reaction is described, in which five-, six-, and -seven-membered rings, tetrasubstituted olefins, bridged bicycles, spirocycles, and benzoxepinones are prepared. Highly selective intermolecular reactions are coupled to a Nazarov cyclization for the effective preparation of cyclopentenones, including the core of modhephene (see scheme). Copyright
Asymmetric hydrogenation of heteroaromatic ketones and cyclic and acyclic enones mediated by Cu(I)-chiral diphosphine catalysts
Shimizu, Hideo,Nagano, Takuto,Sayo, Noboru,Saito, Takao,Ohshima, Takashi,Mashima, Kazushi
scheme or table, p. 3143 - 3146 (2010/03/24)
Copper(I)-catalyzed asymmetric hydrogenation of heteroaromatic ketones, cyclic and acyclic enones is reported. The choice of the chiral diphosphine ligand highly influenced enantiose-lectivity as well as chemoselectivity. Highly enantioselective hydrogenation of ortho-substituted heteroaromatic ketones was achieved using BDPP as the ligand. In the 1,2-selective hydrogenation of acylic enone, SEGPHOS gave higher enantioselectivity than BDPP. On the other hand, the bulky ligand DTBM-SEGPHOS had a 1,4-selective nature, leading to the first highly 1,4-selective and enantioselective hydrogenation of cyclic enones.
Highly enantio- and s-trans C=C bond selective catalytic hydrogenation of cyclic enones: Alternative synthesis of (-)-menthol
Ohshima, Takashi,Tadaoka, Hiroshi,Hori, Kiyoto,Sayo, Noboru,Mashima, Kazushi
scheme or table, p. 2060 - 2066 (2009/04/07)
A highly enantioselective catalytic hydrogenation of cyclic enones was achieved by using the combination of a cationic Rh1 complex, (S)-5,5′-bis{di(3,5-di-tert-butyl-4-methoxyphenylphosphino)}-4, 4′-bi-1,3-benzodioxole (DTBM-SEGPHOS), and (CH2CH 2PPh3Br)2. The presence of an s-cis C=C bond isopropylidene moiety on the cyclic enone influenced the enantioselectivity of the hydrogenation. Thus, the hydrogenation of 3-alkyl-6-isopropylidene-2- cyclohexen-1-one, which contains both s-cis and s-trans enones, proceeded in excellent enantioselectivity (up to 98% ee). To obtain high enantio- and s-trans selectivities, the addition of a halogen source to the cationic Rh complex was the essential step. With the key step of the s-trans selective asymmetric hydrogenation of piperitenone, we demonstrated a new synthetic method for optically pure (-)-menthol via three atom-economical hydrogenations. Moreover, we found that the complete s-trans and s-cis C=C bond selective reactions were also realized by the proper choice of both the chiral ligands and halides.
Flavor and fragrance compositions
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Page/Page column 6, (2008/06/13)
The present invention provides a flavor and fragrance composition which comprises, as the active ingredient, an optically active (1S)-8-mercaptomenthone having an S-form/R-form mixing ratio for the configuration at the 4-position in the range of from 65:35 to 95:5 by weight, wherein the flavor and fragrance composition is for use in food and beverage, fragrances and cosmetics, pharmaceuticals or oral compositions and the like; a product which is scented with the flavor and fragrance composition; and a method for enhancing or modulating odor of the flavor and fragrance composition by adding the optically active (1S)-8-mercaptomenthone.
Lipase-catalyzed resolution of p-menthan-3-ols monoterpenes: Preparation of the enantiomer-enriched forms of menthol, isopulegol, trans- and cis-piperitol, and cis-isopiperitenol
Serra, Stefano,Brenna, Elisabetta,Fuganti, Claudio,Maggioni, Francesco
, p. 3313 - 3319 (2007/10/03)
A study on the enzymic resolution of the most common p-menthan-3-ol monoterpene isomers is described. Enantioenriched alcohols 1, 5, 10, 11 and 12 are obtained by means of the lipase-mediated kinetic acetylation of the corresponding racemic materials. The stereochemical aspects of the enzymic process have been investigated. We found that the structural features of the starting p-menthan-3-ol as well as the kind of lipase used, impacted strongly on the enantioselectivity of the resolution. The potentialities of this approach for preparative purposes are discussed.
Regio- and diastereoselective tandem addition-carbocyclization promoted by sulfanyl radicals on chiral perhydro-1,3-benzoxazines
Pedrosa, Rafael,Andres, Celia,Duque-Soladana, Juan P.,Maestro, Alicia,Nieto, Javier
, p. 2985 - 2990 (2007/10/03)
Radical addition-carbocyclization of 2-allyl-3-acyloyl-substituted perhydro-1,3-benzoxazines readily provides 3,4-disubstituted pyrrolidinone derivatives with total regioselectivity and good diastereoselectivity. The key step of the reaction is a tandem addition-5-exo-cyclization promoted by a sulfanyl radical.
Catalytic osmium-assisted oxidative cleavage of olefins
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, (2008/06/13)
An osmium-assisted process for the oxidative cleavage of oxidizable organic compounds such as unsaturated organic compounds, including alkenes and olefins into aldehydes, carboxylic acids, esters, or ketones. The process uses a metal catalyst comprising osmium and a peroxy compound selected from the group consisting of peroxymonosulfuric acid and salts thereof to oxidatively cleave the oxidizable organic compound. In particular, the process enables aldehydes, carboxylic acids, esters, or ketones to be selectively produced from the corresponding mono-, 1,1-di-, 1,2-di-, tri-, or tetra-substituted olefins in a reaction that produces the result of ozonolysis but with fewer problems. The present invention further provides a process for oxidizing an aldehyde alone or with the osmium in an interactive solvent to produce an ester or carboxylic acid.
