190059-33-7Relevant academic research and scientific papers
Fungi-mediated biotransformation of the isomeric forms of the apocarotenoids ionone, damascone and theaspirane
Serra, Stefano,De Simeis, Davide
, (2019)
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.
Practical synthesis of canthaxanthin
Pi, Shiqing,Xi, Meiyang,Deng, Liping,Xu, Huiting,Feng, Chengjie,Shen, Runpu,Wu, Chunlei
, p. 493 - 497 (2019/11/03)
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.
Selective oxygenation of ionones and damascones by fungal peroxygenases
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)
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.
Total Synthesis of (+)-Granatumine A and Related Bislactone Limonoid Alkaloids via a Pyran to Pyridine Interconversion
Schuppe, Alexander W.,Zhao, Yizhou,Liu, Yannan,Newhouse, Timothy R.
supporting information, p. 9191 - 9196 (2019/06/17)
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.
In Vitro Regio- and Stereoselective Oxidation of β-Ionone by Human Liver Microsomes
Marumoto, Shinsuke,Shimizu, Ryoyu,Tanabe, Genzoh,Okuno, Yoshiharu,Miyazawa, Mitsuo
, p. 292 - 299 (2017/02/26)
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
Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration
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)
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.
Synthesis and in vitro characterization of ionone-based compounds as dual inhibitors of the androgen receptor and NF-κB
Liu, Weiguo,Zhou, Jinming,Geng, Guoyan,Lin, Rongtuan,Wu, Jian Hui
, p. 227 - 234 (2014/04/03)
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.
Facile lipase catalysed syntheses of (S)-(+)-4-hydroxy-β-ionone and (S)-(+)-4-hydroxy-β-damascone: Chiral flavorants and synthons
More, Gauri P.,Bhat, Sujata V.
, p. 4148 - 4149 (2013/07/26)
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
Synthetic analogues of abscisic acid with anti-inflammatory and insulin release stimulation effects on human cells
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Page/Page column 5, (2012/11/06)
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.
Expedient construction of the ziegler intermediate useful for the synthesis of forskolin via consecutive rearrangements
Ye, Heping,Deng, Gang,Liu, Jun,Qiu, Fayang G.
supporting information; experimental part, p. 5442 - 5444 (2010/02/28)
"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
