128121-03-9Relevant academic research and scientific papers
Total synthesis of the alkaloids martinelline and martinellic acid via a hetero Diels-Alder multicomponent coupling reaction
Powell, David A.,Batey, Robert A.
, p. 2913 - 2916 (2002)
(formula presented) A concise synthesis of the guanidine alkaloids, (±)-martinelline and (±)-martinellic acid, using a protic acid catalyzed 2:1 hetero Diels-Alder coupling reaction between N-Cbz 2-pyrroline and methyl 4-aminobenzoate, is described. Protic acid catalysis, rather than Lewis acid catalysis, was necessary to achieve the desired sense of diastereocontrol in the coupling reaction.
Peroxide-shunt substrate-specificity for the Salmonella typhimurium O 2-dependent tRNA modifying monooxygenase (MiaE)
Corder, Andra L.,Subedi, Bishnu P.,Zhang, Siai,Dark, Amanda M.,Foss Jr., Frank W.,Pierce, Brad S.
, p. 6182 - 6196 (2013/10/01)
Post-transcriptional modifications of tRNA are made to structurally diversify tRNA. These modifications alter noncovalent interactions within the ribosomal machinery, resulting in phenotypic changes related to cell metabolism, growth, and virulence. MiaE is a carboxylate bridged, nonheme diiron monooxygenase, which catalyzes the O2-dependent hydroxylation of a hypermodified-tRNA nucleoside at position 37 (2-methylthio-N6- isopentenyl-adenosine(37)-tRNA) [designated ms2i6A 37]. In this work, recombinant MiaE was cloned from Salmonella typhimurium, purified to homogeneity, and characterized by UV-visible and dual-mode X-band EPR spectroscopy for comparison to other nonheme diiron enzymes. Additionally, three nucleoside substrate-surrogates (i6A, Cl2i6A, and ms2i6A) and their corresponding hydroxylated products (io6A, Cl2io 6A, and ms2io6A) were synthesized to investigate the chemo- and stereospecificity of this enzyme. In the absence of the native electron transport chain, the peroxide-shunt was utilized to monitor the rate of substrate hydroxylation. Remarkably, regardless of the substrate (i6A, Cl2i6A, and ms2i6A) used in peroxide-shunt assays, hydroxylation of the terminal isopentenyl-C4-position was observed with >97% E-stereoselectivity. No other nonspecific hydroxylation products were observed in enzymatic assays. Steady-state kinetic experiments also demonstrate that the initial rate of MiaE hydroxylation is highly influenced by the substituent at the C2-position of the nucleoside base (v0/[E] for ms2i6A > i 6A > Cl2i6A). Indeed, the >3-fold rate enhancement exhibited by MiaE for the hydroxylation of the free ms 2i6A nucleoside relative to i6A is consistent with previous whole cell assays reporting the ms2io6A and io6A product distribution within native tRNA-substrates. This observation suggests that the nucleoside C2-substituent is a key point of interaction regulating MiaE substrate specificity.
