- Fungi-mediated biotransformation of the isomeric forms of the apocarotenoids ionone, damascone and theaspirane
-
In this work, we describe a study on the biotransformation of seven natural occurring apocarotenoids by means of eleven selected fungal species. The substrates, namely ionone (α-, β- and γ-isomers), 3,4-dehydroionone, damascone (α- and β-isomers) and theaspirane are relevant flavour and fragrances components. We found that most of the investigated biotransformation reactions afforded oxidized products such as hydroxy- keto- or epoxy-derivatives. On the contrary, the reduction of the keto groups or the reduction of the double bond functional groups were observed only for few substrates, where the reduced products are however formed in minor amount. When starting apocarotenoids are isomers of the same chemical compound (e.g., ionone isomers) their biotransformation can give products very different from each other, depending both on the starting substrate and on the fungal species used. Since the majority of the starting apocarotenoids are often available in natural form and the described products are natural compounds, identified in flavours or fragrances, our biotransformation procedures can be regarded as prospective processes for the preparation of high value olfactory active compounds.
- Serra, Stefano,De Simeis, Davide
-
-
Read Online
- Practical synthesis of canthaxanthin
-
In this study, a novel route for the total synthesis of canthaxanthin is described. The synthesis is firstly based on an epoxidation of α-ionone with metachloroperbenzoic acid to afford the epoxide, followed by conversion of the epoxide to 3-hydroxyl-β-ionone in the presence of sodium methoxide. Next, 3-hydroxyl-C14-aldehyde was obtained by a Darzens condensation with 4-hydroxyl-β-ionone and methyl chloroacetate, which can be converted to 3-hydroxyl-C15-phophonate via a Wittig–Horner condensation with tetraethyl methylenebisphosphonate. Then, a Wittig–Horner condensation with 3-hydroxyl-C15-phosphonate and C10-trienedial resulted in 4,4′-dihydroxyl-β-carotene, followed by an oxidation afforded the target product canthaxanthin. The overall yield of this route is 37% from α-ionone. The synthetic steps are easily operated and are practical for the large-scale production.
- Pi, Shiqing,Xi, Meiyang,Deng, Liping,Xu, Huiting,Feng, Chengjie,Shen, Runpu,Wu, Chunlei
-
p. 493 - 497
(2019/11/03)
-
- Selective oxygenation of ionones and damascones by fungal peroxygenases
-
Apocarotenoids are among the most highly valued fragrance constituents, being also appreciated as synthetic building blocks. This work shows the ability of unspecific peroxygenases (UPOs, EC1.11.2.1) from several fungi, some of them being described recently, to catalyze the oxyfunctionalization of α- and β-ionones and α- and β-damascones. Enzymatic reactions yielded oxygenated products such as hydroxy, oxo, carboxy, and epoxy derivatives that are interesting compounds for the flavor and fragrance and pharmaceutical industries. Although variable regioselectivity was observed depending on the substrate and enzyme, oxygenation was preferentially produced at the allylic position in the ring, being especially evident in the reaction with α-ionone, forming 3-hydroxy-α-ionone and/or 3-oxo-α-ionone. Noteworthy were the reactions with damascones, in the course of which some UPOs oxygenated the terminal position of the side chain, forming oxygenated derivatives (i.e., the corresponding alcohol, aldehyde, and carboxylic acid) at C-10, which were predominant in the Agrocybe aegerita UPO reactions, and first reported here.
- Aranda, Carmen,Babot, Esteban D.,Del R?o, José C.,Gutiérrez, Ana,Hofrichter, Martin,Kiebist, Jan,Mart?nez, Angel T.,Scheibner, Katrin,Ullrich, René
-
p. 5375 - 5383
(2020/06/08)
-
- Total Synthesis of (+)-Granatumine A and Related Bislactone Limonoid Alkaloids via a Pyran to Pyridine Interconversion
-
We report the first total synthesis of (+)-granatumine A, a limonoid alkaloid with PTP1B inhibitory activity, in ten steps. Over the course of this study, two key methodological advances were made: a cost-effective procedure for ketone α,β-dehydrogenation using allyl-Pd catalysis, and a Pd-catalyzed protocol to convert epoxyketones to 1,3-diketones. The central tetrasubstituted pyridine is formed by a convergent Knoevenagel condensation and carbonyl-selective electrocyclization cascade, which was followed by a direct transformation of a 2H-pyran to a pyridine. These studies have led to the structural revision of two members of this family.
- Schuppe, Alexander W.,Zhao, Yizhou,Liu, Yannan,Newhouse, Timothy R.
-
supporting information
p. 9191 - 9196
(2019/06/17)
-
- In Vitro Regio- and Stereoselective Oxidation of β-Ionone by Human Liver Microsomes
-
The metabolism of the norisoprenoid β-ionone was investigated in vitro using human liver microsomes and 11 different recombinant cytochrome P450 enzymes expressed in Trichoplusia ni cells. β-Ionone was found to be oxidized via 4S-hydroxylation by CYP2B6 i
- Marumoto, Shinsuke,Shimizu, Ryoyu,Tanabe, Genzoh,Okuno, Yoshiharu,Miyazawa, Mitsuo
-
p. 292 - 299
(2017/02/26)
-
- Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration
-
All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation.
- Zhang, Jianye,Dong, Zhiqian,Mundla, Sreenivasa Reddy,Hu, X. Eric,Seibel, William,Papoian, Ruben,Palczewski, Krzysztof,Golczak, Marcin
-
supporting information
p. 477 - 491
(2015/01/30)
-
- Synthesis and in vitro characterization of ionone-based compounds as dual inhibitors of the androgen receptor and NF-κB
-
Current therapeutic strategy for advanced prostate cancer is to suppress the androgen receptor (AR) signaling. However, lethal castration-resistant prostate cancer (CRPC) arises due to AR reactivation via multiple mechanisms, including mutations in the AR and cross-talk with other pathways such as NF-κB. We have previously identified two ionone-based antiandrogens (SC97 and SC245), which are full antagonists of the wild type and the clinically-relevant T877A, W741C and H874Y mutated ARs. Here, we discovered SC97 and SC245 also inhibit NF-κB. By synthesizing a series of derivatives of these two compounds, we have discovered a novel compound 3b that potently inhibits both AR and NF-κB signalling, including the AR F876L mutant. Compound 3b showed low micromolar antiproliferative activites in C4-2B and 22Rv1 cells, which express mutated ARs and are androgen-independent, as well as DU-145 and PC-3 cells, which exhibit constitutively activated NF-κB signalling. Our studies indicate 3b is effective against the CRPC cells.
- Liu, Weiguo,Zhou, Jinming,Geng, Guoyan,Lin, Rongtuan,Wu, Jian Hui
-
p. 227 - 234
(2014/04/03)
-
- Facile lipase catalysed syntheses of (S)-(+)-4-hydroxy-β-ionone and (S)-(+)-4-hydroxy-β-damascone: Chiral flavorants and synthons
-
Enantioselective syntheses of (S)-(+)-4-hydroxy-β-ionone and (S)-(+)-4-hydroxy-β-damascone have been achieved through pig pancreatic lipase catalysed trans-esterification. These molecules find utility as constituent in fruit-type fragrance and flavor form
- More, Gauri P.,Bhat, Sujata V.
-
p. 4148 - 4149
(2013/07/26)
-
- Synthetic analogues of abscisic acid with anti-inflammatory and insulin release stimulation effects on human cells
-
Compound of formula (I) as drug, having abscisic acid antagonist activity and insulin release stimulating activity, in particular for treatment of inflammatory pathologies of type 2 diabetes. Compound of formula (I) wherein R is selected from hydrogen e =O groups, R1 is selected from -H e -OH, R2 is selected from groups having one of following structural formulae (II), (III): wherein X is selected from -OH, optionally substituted alkylamino-, arylamino-, alkylarylamino- or arylalkylamino-, alkoxy-, aryloxy-, alkylaryloxy- or arylalkoxy- groups, with said groups having from one to eight carbon atoms, with the alkyl chains of such groups being optionally branched, containing unsaturations or forming rings, said groups optionally containing atoms or functionalities different from C, salts of said compound or pharmaceutically acceptable precursors thereof, metabolites, hydrates or solvates thereof, for use as a drug.
- -
-
Page/Page column 5
(2012/11/06)
-
- Expedient construction of the ziegler intermediate useful for the synthesis of forskolin via consecutive rearrangements
-
"Chemical Equation Presented" The Ziegler Intermediate, useful for the total synthesis of forskolin, was synthesized in 10 reaction steps starting from commercially available a-lonone. This highly efficient synthesis relies on the success of two consecuti
- Ye, Heping,Deng, Gang,Liu, Jun,Qiu, Fayang G.
-
supporting information; experimental part
p. 5442 - 5444
(2010/02/28)
-
- A convenient cross-metathesis approach to trisporins
-
Three series of trisporins have been prepared using a strategy in which a cross-metathesis is the key step. This reaction has proved to be highly regioselective, allowing the combination of α- or β-ionone derivatives having a 1,1-disustituted olefin with
- López-Sánchez, Cristóbal,Hernández-Cervantes, Carmen,Rosales, Antonio,álvarez-Corral, Míriam,Mu?oz-Dorado, Manuel,Rodríguez-García, Ignacio
-
scheme or table
p. 9542 - 9549
(2010/02/27)
-
- Synthesis, olfactory evaluation, and determination of the absolute configuration of the 3,4-didehydroionone stereoisomers
-
The synthesis of 3,4-didehydroionone isomers 4, (+)-6, and (-)-6 and of 3,4-didehydro-7,8-dihydroionone isomers 5, (+)-7, and (-)-7 was accomplished starting from commercially available racemic α-ionone (1). Their preparation of the racemic forms 4-7 was first achieved by mean of a number of chemo- and regioselective reactions (Schemes 1 and 2). The enantio- and diastereoselective lipase-mediated kinetic acetylation of 4-hydroxy-γ- ionone (10a/10b) provided 4-hydroxy-γ-ionone (+)-10a/(±)-10b and (+)-4-(acetyloxy)-γ-ionone ((+)12b) (Scheme 3). The latter compounds were used as starting materials to prepare the 3,4-didehydro-γ-ionones (+)- and (-)-6 and the 3,4-didehydro-7,8-dihydro-γ-ionones (+)- and (-)-7 in enantiomer-enriched form. The absolute configuration of (+)-12b was determine by chemical correlation with (+)-(6S)-γ-ionone ((+)-3) and with (-)-(6S)-α-ionone ((-)-1) therefore allowing to assign the (S)-configuration to (+)-6 and (+)-7. Olfactory evaluation of the above described 3,4-didehydroionone isomers shows a significant difference between the enantiomers and regioisomers both in fragrance feature and in detection threshold (Table).
- Serra, Stefano,Fuganti, Claudio,Brenna, Elisabetta
-
p. 1110 - 1122
(2007/10/03)
-
- Enantioselective synthesis of 1(R)-hydroxypolygodial
-
Enantioselective preparation of 1(R)-hydroxypolygodial (5) has been achieved starting from α-ionone through a synthetic strategy involving a Corey-Bakshi-Shibata oxazaborolidine-mediated reduction and a stereoselective Diels-Alder reaction as key steps.
- Della Monica, Carmela,Della Sala, Giorgio,D'Urso, Deborah,Izzo, Irene,Spinella, Aldo
-
p. 4061 - 4063
(2007/10/03)
-
- Efficient electrophilic and nucleophilic epoxidations utilizing a sulfonylperoxy radical and peroxysulfate species
-
Reaction of superoxide anion radical (O2-. with o-nitrobenzenesulfonyl chloride yields a o-nitrobenzenesulfonyl peroxy radical with strong oxidizing ability, which is capable of oxidizing aryl methylene moieties to aryl ketones and relatively electron-rich alkenes regioselectively to epoxides. The oxidizing species is tentatively attributed to the o-nitrobenzenesulfonyl peroxy radical of structure 1. Tetrabutylammonium peroxydisulfate (TBA)2S2O8, 2) was prepared by the reaction of tetrabutylammonium hydrogen sulfate with potassium peroxydisulfate. The epoxidation of enals and enones, such as α,β-unsaturated aldehydes or ketones, was efficiently achieved with 2 in the presence of hydrogen peroxide and base in acetonitrile or in methanol at 25°C. A base-sensitive substrate, such as cinnamaldehyde, could be successfully epoxidized under mild reaction conditions and in short reaction time.
- Park, Min Young,Yang, Seung Gak,Kim, Yong Hae
-
p. 431 - 436
(2007/10/03)
-
- C-15 phosphonate reagent compositions for the manufacture of compounds such as canthaxanthin and methods of synthesizing the same
-
The present invention describes novel C-15 allenic phosphonate reagent compositions of the formula: STR1 The invention also describes novel C-15 allylic phosphonate reagent compositions of the formula: STR2 The invention also describes methods of preparing canthaxanthin, the phosphonate reagent compositions, and a tertiary propargylic alcohol of the formula: STR3
- -
-
-
- A versatile cobalt(II)-Schiff base catalyzed oxidation of organic substrates with dioxygen: Scope and mechanism
-
Cobalt(II) complex 1a-f derived from Schiff bases act as efficient catalysts during the oxidation of wide range of organic substrates(e.g. alkenes, alcohols, benzylic compounds and aliphatic hydrocarbons) with dioxygen in the presence of aliphatic aldehydes or ketones or ketoesters. EPR studies on 1a-f complexes suggest that the aliphatic carbonyl compounds promote the formation of a cobalt(II)-superoxo species responsible for the oxidation of organic compounds. These studies also demonstrate the role of ligands on cobalt in controlling the chemoselectivity of these oxidations. A plausible mechanistic rational is also provided for these oxidations.
- Punniyamurthy,Bhatia, Beena,Reddy, M. Madhava,Maikap, Golak C.,Iqbal, Javed
-
p. 7649 - 7670
(2007/10/03)
-
- A Halide-Free Method for Olefin Epoxidation with 30% Hydrogen Peroxide
-
A catalytic system consisting of sodium tungstate dihydrate, (aminomethyl) phosphonic acid, and methyltrioctylammonium Hydrogensulfate, effects the epoxidation of olefins using 30% hydrogen peroxide with a substrate-to-catalyst molar ratio of 50 - 500. The reaction proceeds in high yield without solvents, or, alternatively, with added toluene under entirely halide-free conditions. Lipophilic ammonium hydrogensulfate, which replaces the conventional chloride, and an (α-aminoalkyl)phosphonic acid are crucial for the high reactivity. This method is operationally simple, environmentally benign, and much more economical than the oxidation with m-chloroperbenzoic acid, allowing for a large-scale preparation of epoxides. Various substrates including terminal olefins, 1,1- and 1,2-disubstituted olefins, cyclic olefins, and tri- and tetrasubstituted olefins as well as allylic alcohols, esters, α,β-unsaturated ketones, and ethers can be epoxidized in high yield. The scope and limitations of this new reaction system are discussed.
- Sato, Kazuhiko,Aoki, Masao,Ogawa, Masami,Hashimoto, Tadashi,Panyella, David,Noyori, Ryoji
-
p. 905 - 915
(2007/10/03)
-
- -
-
The electrocyclisation of allenyldiene easily obtained from hydroxy-β-ionone has been studied with the aim to set up an efficient access to polyhydroxylated decalinic systems. Some aspects of the stereoselectivity of this reaction are discussed and the tr
- Leclaire,Jean,Lopez,Ricard,Plessix,Lallemand
-
p. 6983 - 6998
(2007/10/02)
-
- Microbial synthesis of optically pure (R)-2,4,4-trimethyl-3-(2'-hydroxyethyl)-cyclohex-2-en-1-ol, a new and versatile chiral building block for terpene synthesis
-
The hydroxylation of 2,4,4-trimethyl-3-(2'-hydroxyethyl)-2-cyclohexene by Mucor plumbeus, after usual work up and a subsequent single crystallization, gave the corresponding optically pure (1R)-hydroxy synthon.
- Aranda,Bertranne,Azerad,Maurs
-
p. 675 - 678
(2007/10/02)
-
- A Novel Method for the Preparation of Acid-Sensitive Epoxides from Olefins with the Combined Use of Molecular Oxygen and Aldoacetal Catalyzed by a Cobalt(II) Complex
-
An efficient synthesis of acid-sensitive epoxides, such as chromene oxide or epoxide of γ,δ-unsaturated alcohol, was successfully achieved by the oxygenation of corresponding olefins with the combined use of an atmospheric pressure of molecular oxygen and aldoacetal catalyzed by a cobalt(II) complex coordinated with the 1,3-diketone ligand.The reactions proceeded under mild and neutral conditions, and the desired epoxides were obtained in good yields.Neither overoxidation nor decomposition of the formed epoxide was observed under the present reaction conditions.Furthermore, various silyl enol ethers and silyl ketene acetals, acid-sensitive compounds, were also smoothly monooxygenated into the corresponding α-hydroxy ketones and α-hydroxy carboxylic acid esters, respectively.
- Yorozu, Kiyotaka,Takai, Toshihiro,Yamada, Tohru,Mukaiyama, Teruaki
-
p. 2195 - 2202
(2007/10/02)
-
- Aerobic Epoxidation of Olefins Catalyzed by Cobalt(II) Complex Using Propionaldehyde Diethyl Acetal as a Reductant
-
In the presence of bis(3-methyl-2,4-pentanedionato)cobalt(II) complex catalyst, various trisubstituted olefins are smoothly monooxygenated into the corresponding epoxides in high yields under neutral conditions by the combined use of molecular oxygen and propionaldehyde diethyl acetal.
- Mukaiyama, Teruaki,Yorozu, Kiyotaka,Takai, Toshihiro,Yamada, Tohru
-
p. 439 - 442
(2007/10/02)
-
- Practical Total Synthesis of (+/-)-Strigol
-
An improved total synthesis of racemic strigol (1) and 4'-epistrigol (21) from α-ionone in 10 (4.4percent overall yield) or 12 steps (6.8percent overall yield) by recycling isomer 16 is described which is applicable on a multigram scale with a minimum of
- Brooks, Dee W.,Bevinakatti, H. S.,Kennedy, Eileen,Hathaway, Jim
-
p. 628 - 632
(2007/10/02)
-
- Facile and Regioselective Epoxidations of Olefins with a Peroxysulfur Intermediate Generated from Superoxide Anion (O2-.) and Nitrobenzenesulfonyl Chlorides
-
A peroxysulfur intermediate generated from the reaction of o- or p-nitrobenzenesulfonyl chloride with superoxide anion (O2-.) is found to be an excellent oxidizing reagent for the facile and regioselective epoxidation of olefins at -35 deg C.
- Kim, Yong Hae,Chung, Bong Chul
-
p. 1562 - 1564
(2007/10/02)
-
- 1-(2,6,6-Trimethyl-3-hydroxy-1-cyclohexen-1-yl)-3-methyl-penta-1,4-diene[or 1-yn-4-EN]-3-ols
-
A total synthesis of canthaxanthin, a known food coloring agent from alpha or retro ionone.
- -
-
-