67662-04-8Relevant academic research and scientific papers
Dehydroxymethylation of alcohols enabled by cerium photocatalysis
Zhang, Kaining,Chang, Liang,An, Qing,Wang, Xin,Zuo, Zhiwei
supporting information, p. 10556 - 10564 (2019/08/20)
Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.
Dehydroxymethylation of Alcohols Enabled by Cerium Photocatalysis
Zhang, Kaining,Chang, Liang,An, Qing,Wang, Xin,Zuo, Zhiwei
supporting information, p. 10556 - 10564 (2019/08/28)
Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.
Exploration of a potential difluoromethyl-nucleoside substrate with the fluorinase enzyme
Thompson, Stephen,McMahon, Stephen A.,Naismith, James H.,O'Hagan, David
, p. 37 - 41 (2015/12/08)
The investigation of a difluoromethyl-bearing nucleoside with the fluorinase enzyme is described. 5′,5′-Difluoro-5′-deoxyadenosine 7 (F2DA) was synthesised from adenosine, and found to bind to the fluorinase enzyme by isothermal titration calorimetry with similar affinity compared to 5′-fluoro-5′-deoxyadenosine 2 (FDA), the natural product of the enzymatic reaction. F2DA 7 was found, however, not to undergo the enzyme catalysed reaction with l-selenomethionine, unlike FDA 2, which undergoes reaction with l-selenomethionine to generate Se-adenosylselenomethionine. A co-crystal structure of the fluorinase and F2DA 7 and tartrate was solved to 1.8 ?, and revealed that the difluoromethyl group bridges interactions known to be essential for activation of the single fluorine in FDA 2. An unusual hydrogen bonding interaction between the hydrogen of the difluoromethyl group and one of the hydroxyl oxygens of the tartrate ligand was also observed. The bridging interactions, coupled with the inherently stronger C-F bond in the difluoromethyl group, offers an explanation for why no reaction is observed.
Structure of the epigenetic oncogene MMSET and inhibition by N-alkyl sinefungin derivatives
Tisi, Dominic,Chiarparin, Elisabetta,Tamanini, Emiliano,Pathuri, Puja,Coyle, Joseph E.,Hold, Adam,Holding, Finn P.,Amin, Nader,Martin, Agnes C. L.,Rich, Sharna J.,Berdini, Valerio,Yon, Jeff,Acklam, Paul,Burke, Rosemary,Drouin, Ludovic,Harmer, Jenny E.,Jeganathan, Fiona,Van Montfort, Rob L. M.,Newbatt, Yvette,Tortorici, Marcello,Westlake, Maura,Wood, Amy,Hoelder, Swen,Heightman, Tom D.
, p. 3093 - 3105 (2016/11/29)
The members of the NSD subfamily of lysine methyl transferases are compelling oncology targets due to the recent characterization of gain-of-function mutations and translocations in several hematological cancers. To date, these proteins have proven intrac
Approaches to isozyme-specific inhibitors. 16. A novel methyl-C5' covalent adduct of L-ethionine and β,γ-imido-ATP as a potent multisubstrate inhibitor of rat methionine adenosyltransferase
Vrudhula,Kappler,Afshar,Ginell,Lessinger,Hampton
, p. 885 - 890 (2007/10/02)
N6,N6-Dibenzoyl-2',3'-O-isopropylideneadenosine, which is readily synthesized by one-pot 5'-O-trimethylsilylation, N6-benzoylation, and desilylation, was coverted to the corresponding 5'-aldehyde. This was treated with CH2 = CHMgBr to afford, after debenzoylation, a 1:3 mixture of the 5'S and 5'R epimers, respectively, of 5'-C-vinyl2',3'-O-isopropylideneadenosine. The configurations were established by single-crystal X-ray diffraction analysis of the 5'R epimer. Hydroboration of the 5'-O-tetrahydropyranyl derivative of the mixed epimeric 5'-C-vinyl nucleosides readily furnished 5'(S,R)-C-(2-hydroxyethyl)-2',3'-O-isopropylideneadenosine. Treatment of the 5'(S,R)-C-(2-O-tosyl) derivative of this with disodium L-homocysteinate permitted facile introduction of the L-ethionine system. By means of methods developed earlier in the synthesis of homologous methionine-ATP adducts, the α-amino acid group was protected, a β,γ-imidotriphosphoryl group was introduced at O5', and blocking groups were removed to give the title adduct as a 2:3 mixture of its two 5' epimers. It was a powerful inhibitor [K(M)(ATP)/K(i) = 520 and 340] of the M-2 (normal tissue) and M-T (hepatoma tissue) forms, respectively, of the title enzyme and displayed predominantly competitive kinetics with the two substrates L-methionine and MgATP. It inhibited M-2 and M-T slightly less effectively than its homologue possessing one less CH2 between sulfur and C5' and gave kinetic evidence of an increased tendency to form L-methionine-enzyme-adduct and MgATP-enzyme-adduct complexes.
