14398-34-6Relevant academic research and scientific papers
Characterization of CYP154F1 from Thermobifida fusca YX and Extension of Its Substrate Spectrum by Site-Directed Mutagenesis
Rühlmann, Ansgar,Groth, Georg,Urlacher, Vlada B.
, p. 478 - 485 (2018)
Previous studies on cytochrome P450 monooxygenases (CYP) from family 154 reported their substrate promiscuity and high activity. Hence, herein, the uncharacterized family member CYP154F1 is described. Screening of more than 100 organic compounds revealed
The crystal structure of the versatile cytochrome P450 enzyme CYP109B1 from Bacillus subtilis
Zhang, Aili,Zhang, Ting,Hall, Emma A.,Hutchinson, Sean,Cryle, Max J.,Wong, Luet-Lok,Zhou, Weihong,Bell, Stephen G.
, p. 869 - 881 (2015)
The crystal structure of the versatile CYP109B1 enzyme from Bacillus subtilis has been solved at 1.8 ? resolution. This is the first structure of an enzyme from this CYP family, whose members are prevalent across diverse species of bacteria. In the crysta
DoE (Design of Experiments) assisted allylic hydroxylation of enones catalysed by a copper-aluminium mixed oxide
Garcia-Cabeza, Ana Leticia,Marin-Barrios, Ruben,Azarken, Redouan,Moreno-Dorado, F. Javier,Ortega, Maria J.,Vidal, Hilario,Gatica, Jose M.,Massanet, Guillermo M.,Guerra, Francisco M.
, p. 8307 - 8314 (2013)
The allylic hydroxylation of enones using dioxygen as the oxidant has been studied. The reaction was first examined in the absence of any catalyst, using β-ionone as a model substrate. Then a new copper-aluminium mixed oxide, Cu-Al Ox, was prepared and ch
Studies on the enantioselective oxidation of β-ionone with a whole E. coli system expressing cytochrome P450 monooxygenase BM3
Zehentgruber, Daniela,Urlacher, Vlada B.,Luetz, Stephan
, p. 62 - 64 (2012)
Recombinant Escherichia coli cells, expressing an NADH-dependent cytochrome P450 monooxygenase BM-3 mutant, were used for the hydroxyalation of the sesquiterpenoid β-ionone to (R)-4-hydroxy-β-ionone. The decrease in enantioselectivity of cytochrome P450 monooxygenase BM-3 catalyzed hydroxylation of β-ionone can be ascribed to the overoxidation of the desired product. In this initial study we report, that by addressing reaction conditions the enantiomeric excess can be increased and the overoxidation can be reduced. Furthermore, we report herein the kinetic resolution of racemic 4-hydroxy-β-ionone using the same P450 monooxygenase for the production of (S)-4-hydroxy-β-ionone. Although the enantioselectivity of the enzyme is rather low for this reaction, this reaction could be of interest with improved P450 BM-3 variants. Both systems need further investigations and optimizations for preparative application.
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.
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
, 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.
β-Carotene autoxidation: Oxygen copolymerization, non-vitamin A products, and immunological activity
Burton, Graham W.,Daroszewski, Janusz,Nickerson, James G.,Johnston, James B.,Mogg, Trevor J.,Nikiforov, Grigory B.
supporting information, p. 305 - 316 (2014/05/06)
Carotenoids are reported to have immunological effects independent of vitamin A activity. Although antioxidant activity has been suggested as a basis of action, the ability of carotenoids to autoxidize to numerous non-vitamin A products with immunological activity is an alternative yet to be fully explored. We have undertaken a systematic study of β-carotene autoxidation and tested the product mixture for immunological activity. Autoxidation proceeds predominantly by oxygen copolymerization, leading to a defined, reproducible product corresponding to net uptake of almost 8 molar equivalents of oxygen. The product, termed OxC-beta, empirical formula C40H60O 15 versus C40H56 for β-carotene, contains more than 30% oxygen (w/w) and 85% β-carotene oxygen copolymers (w/w) as well as minor amounts of many C8-C18 norisoprenoid compounds. No vitamin A or higher molecular weight norisoprenoids are present. The predominance of polymeric products has not been reported previously. The polymer appears to be a less polymerized form of sporopollenin, a biopolymer found in exines of spores and pollen. Autoxidations of lycopene and canthaxanthin show a similar predominance of polymeric products. OxC-beta exhibits immunological activity in a PCR gene expression array, indicating that carotenoid oxidation produces non-vitamin A products with immunomodulatory potential.
