6666-75-7Relevant articles and documents
Synthesis of (E)-α,β-unsaturated carboxylic esters derivatives from cyanoacetic acid via promiscuous enzyme-promoted cascade esterification/Knoevenagel reaction
Wilk, Monika,Trzepizur, Damian,Koszelewski, Dominik,Brodzka, Anna,Ostaszewski, Ryszard
, (2019/02/25)
A new enzymatic protocol based on lipase-catalyzed cascade toward (E)-α,β-unsaturated carboxylic esters is presented. The proposed methodology consists of elementary organic processes starting from acetals and cyanoacetic acid leading to the formation of desired products in a cascade sequence. The combination of enzyme promiscuous abilities gives a new opportunity to synthesize complex molecules in the one-pot procedure. Results of studies on the influence of an enzyme type, solvent, and temperature on the cascade reaction course are reported. The presented methodology provides meaningful qualities such as significantly simplified process, excellent E-selectivity of obtained products and recycling of a biocatalyst.
Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors
Park, Chun-Ho,Lee, Chulho,Yang, Jee Sun,Joe, Bo-Young,Chun, Kwangwoo,Kim, Hyuntae,Kim, Hye Yun,Kang, Jong Soon,Lee, Jangik I.,Kim, Myung-Hwa,Han, Gyoonhee
, p. 2655 - 2660 (2014/06/09)
Inactivation of the NF-κB signaling pathway by inhibition of IKKβ is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKβ inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-α, which are well-known inflammatory responses generated by activated NF-κB. However, no inhibitory activity against IKKβ was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1 μM. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML.
A substrate-driven approach to determine reactivities of α,β-unsaturated carboxylic esters towards asymmetric bioreduction
Tasnádi, Gábor,Winkler, Christoph K.,Clay, Dorina,Sultana, Nargis,Fabian, Walter M. F.,Hall, Mélanie,Ditrich, Klaus,Faber, Kurt
supporting information; experimental part, p. 10362 - 10367 (2012/10/08)
The degree of C=C bond activation in the asymmetric bioreduction of α,β-unsaturated carboxylic esters by ene-reductases was studied, and general recommendations to render these "borderline-substrates" more reactive towards enzymatic reduction are proposed. The concept of "supported substrate activation" was developed. In general, an additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates, and α-cyano groups showed little effect. The alcohol moiety of the ester functionality was found to have a strong influence on the reaction rate. Overall, activities were determined by both steric and electronic effects. Biotransformation: The asymmetric bioreduction of α,β-unsaturated carboxylic esters by ene-reductases could be tuned by varying the degree of C=C bond activation (see scheme). An additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates. Copyright
