89-82-7Relevant academic research and scientific papers
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.
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.
Mo(CO)6-promoted facile deoxygenation of α,β-epoxy ketones and α,β-epoxy esters
Patra, Asit,Bandyopadhyay, Mausumi,Mal, Dipakranjan
, p. 2355 - 2357 (2007/10/03)
Deoxygenation of α,β-epoxy ketones and α,β-epoxy esters is accomplished in high yields under mild and neutral conditions by the use of Mo(CO)6.
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.
