1721-12-6Relevant articles and documents
Probing riboswitch-ligand interactions using thiamine pyrophosphate analogues
Chen, Liuhong,Cressina, Elena,Dixon, Neil,Erixon, Karl,Agyei-Owusu, Kwasi,Micklefield, Jason,Smith, Alison G.,Abell, Chris,Leeper, Finian J.
, p. 5924 - 5931 (2012)
The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch-ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.
Transition-Metal-Free Synthesis of Pyridine Derivatives by Thermal Cyclization of N -Propargyl Enamines
Chikayuki, Yuya,Higashiyama, Kimio,Kirita, Akiko,Matsuo, Natsuko,Miyashige, Takakane,Sasaki, Shigeru,Teramoto, Hiroyoshi,Yamauchi, Takayasu,Yonekawa, Shiori
, p. 1113 - 1121 (2020/04/01)
A transition-metal-free synthesis of pyridine derivatives by 6- endo - dig cyclization of N -propargyl enamines was developed. This method is environmentally friendly and is a high atom economy reaction that is easily accessed to provide pyridine derivatives in moderate to good yield by heating N -propargyl enamines in solvent without additives. The total synthesis of onychine was achieved in 51% yield in only two steps by using this method.
Metal-free michael-addition-initiated three-component reaction for the regioselective synthesis of highly functionalized pyridines: Scope, mechanistic investigations and applications
Allais, Christophe,Lieby-Muller, Frederic,Rodriguez, Jean,Constantieux, Thierry
supporting information, p. 4131 - 4145 (2013/07/19)
A metal-free and completely regioselective three-component synthesis of highly functionalized pyridines from 1,3-dicarbonyl derivatives and Michael acceptors has been achieved. Activated Michael acceptors, that is, β,γ-unsaturated α-oxo carbonyl derivatives, were utilized, allowing substitution at the 4-position and remarkable functional diversity at the 2-position of the pyridine ring. The scope and limitations of this environmentally friendly domino reaction are disclosed, with full experimental data, and the results of mechanistic investigations are discussed. The three-component synthesis of polysubstituted pyridines starting from 1,3-dicarbonyl compounds, α,β-unsaturated carbonyl derivatives and ammonium acetate has been studied, including the scope and mechanism. This methodology is a rare example of a totally regioselective multicomponent access to highly substituted pyridines that complies with many of the stringent criteria of sustainable chemistry. Copyright
