149733-71-1Relevant articles and documents
Tandem oxidation-dehydrogenation of (hetero)arylated primary alcohols via perruthenate catalysis
Bettencourt, Christian J.,Chow, Sharon,Moore, Peter W.,Read, Christopher D.G.,Jiao, Yanxiao,Bakker, Jan Peter,Zhao, Sheng,Bernhardt, Paul V.,Williams, Craig M.
, p. 652 - 659 (2021/09/08)
Tandem oxidative-dehydrogenation of primary alcohols to give a,b-unsaturated aldehydes in one pot are rare transformations in organic synthesis, with only two methods currently available. Reported herein is a novel method using the bench-stable salt methyltriphenylphosphonium perruthenate (MTP3), and a new co-oxidant NEMO&middoPF6 (NEMO = N-ethyl-N-hydroxymorpholinium) which provides unsaturated aldehydes in low to moderate yields. The Ley-Griffith oxidation of (hetero)arylated primary alcohols with N-oxide co-oxidants NMO (NMO = N-methylmorpholine N-oxide)/NEMO, is expanded by addition of the N-oxide salt NEMO&middoPF6 to convert the intermediate saturated aldehyde into its unsaturated counterpart. The discovery, method development, reaction scope, and associated challenges of this method are highlighted. The conceptual value of late-stage dehydrogenation in natural product synthesis is demonstrated via the synthesis of a polyene scaffold related to auxarconjugatin B.
Substrate-Controlled Chemo-/Enantioselective Synthesis of α-Benzylated Enals and Chiral Cyclopropane-Fused 2-Chromanone Derivatives
Byeon, Huimyoung,Ryu, Sunghyeon,Yoo, Eun Jeong,Yang, Jung Woon
supporting information, p. 5085 - 5091 (2021/09/20)
Substrate-controlled cascade reactions between α,β-unsaturated aldehydes or their analogues and 2,4-dinitrobenzyl chloride in the presence of a chiral secondary amine as the catalyst and base were developed, to obtain a broad spectrum of α-benzylated enals and enantioenriched cyclopropane-fused chroman-2-one derivatives. The cyclopropane-tethered iminium ion clearly served as a key intermediate in these reactions to trigger stereochemical outcomes, one of which was supported by a control experiment. (Figure presented.).
Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics
Buijs, Ned,Campagna, Roberto,Emanuelli, Monica,Gao, Yongzhi,Innocenti, Paolo,Jespers, Willem,Martin, Nathaniel I.,Parsons, Richard B.,Sartini, Davide,Van Haren, Matthijs J.,Van Westen, Gerard J. P.,Zhang, Yurui,Gutiérrez-De-Terán, Hugo
, p. 12938 - 12963 (2021/09/11)
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-l-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.
