13689-16-2Relevant academic research and scientific papers
Towards a characterization of the structural determinants of specificity in the macrocyclizing thioesterase for deoxyerythronolide B biosynthesis
Argyropoulos, Panos,Bergeret, Fabien,Pardin, Christophe,Reimer, Janice M.,Pinto, Atahualpa,Boddy, Christopher N.,Schmeing, T. Martin
, p. 486 - 497 (2016/02/05)
Type I polyketide synthases (PKSs) are giant multidomain proteins that synthesize many therapeutics and other natural products. The synthesis proceeds by a thiotemplate mechanism whereby intermediates are covalently attached to the PKS. The release of the final polyketide is catalyzed by the terminal thioesterase (TE) domain through hydrolysis, transesterification, or macrocyclization. The PKS 6-deoxyerythronolide B synthase (DEBS) produces the 14-membered macrolide core of the clinically important antibiotic erythromycin. The TE domain of DEBS (DEBS TE) has well-established, empirically-defined specificities for hydrolysis or macrocyclization of native and modified substrates. We present efforts towards understanding the structural basis for the specificity of the thioesterase reaction in DEBS TE using a set of novel diphenyl alkylphosphonates, which mimic substrates that are specifically cyclized or hydrolyzed by DEBS TE. We have determined structures of a new construct of DEBS TE alone at 1.7 ?, and DEBS TE bound with a simple allylphosphonate at 2.1 ? resolution. Other, more complex diphenyl alkylphosphonates inhibit DEBS TE, but we were unable to visualize these faithful cyclization analogs in complex with DEBS TE. This work represents a first step towards using DEBS TE complexed with sophisticated substrate analogs to decipher the specificity determinants in this important reaction.
Mild and efficient Cs2CO3-promoted synthesis of phosphonates
Cohen, Richard J.,Fox, Daniel L.,Eubank, Jarrod F.,Salvatore, Ralph Nicholas
, p. 8617 - 8621 (2007/10/03)
A mild and convenient synthesis for phosphonates using cesium carbonate (Cs2CO3), tetrabutylammonium iodide (TBAI) and DMF was developed at room temperature. Numerous dialkyl phosphites were screened using a diverse array of alkyl halides and these reaction conditions were found to be highly efficient producing various phosphonates exclusively in moderate to high yields.
One-pot synthesis of unsymmetrical aryl methylphosphinates by insertion of dichlorophosphines into the O-Me bond of anisoles
Baccolini, Graziano,Boga, Carla
, p. 6121 - 6124 (2007/10/03)
This letter describes a new one-pot method for the synthesis of unsymmetrical aryl methylphoshinates by insertion of phosphorus moiety into the O-Me bond of anisoles. These products are very difficult to obtain with other reported methods requiring several steps.
