WE HAVE ALSO BEEN SUCCESSFUL WITH THE CHEMICAL SYNTHESIS OF DIHYDROXYACETONE MONOPHOSPHATE (DHAP). ALTHOUGH THE CONSTRUCTION OF DIHYDROXYACETONE MONOPHOSPHATE (DHAP) HAS BEEN REPORTED, THE SYNTHETIC ROUTE DOES NOT LEND ITSELF TO STABLE ISOTOPE LABELING AND IS LENGTHY AND INEFFICIENT. USING E. J. COREY'S BASE COMPLEX, S-BULI/KOT-BU (IN EFFECT S-BUK), METALLATION OF THE TERT-BUTYL METHYL ETHER IS NEARLY QUANTITATIVE. TREATMENT OF 13CO2 WITH THIS MIXTURE YIELDED THE DIPROTECTED DIHYDROXYACETONE IN 50% YIELD. OVERALL, THIS PROCESS REPRESENTS A 2-STEP SYNTHESIS FROM LABELED METHANOL (METHANOL IS, IN TURN, OBTAINED FROM 13CO). WE WILL ATTEMPT TO CONVERT THIS MATERIAL TO DHAP USING POCL3 IN THE PRESENCE OF A CATALYTIC AMOUNT OF ACID. THE CYCLIC PHOSPHATE INTERMEDIATE HYDROLYSES TO DHAP WHEN THE PH IS ADJUSTED TO ~7.5. WE HAVE ALSO CONVERTED 13CO2 TO THE T-BU PROTECTED GYCOLIC ACID IN ~80% YIELD. SMOOTH CONVERSION TO THE ACID CHLORIDE WAS ACCOMPLISHED USING OXALYL CHLORIDE. TREATMENT OF THE ACID CHLORIDE WITH DIAZOMETHANE AFFORDS THE AZOKETONE IN QUANTITATIVE YIELD. ADDITION OF DIBENZYL PHOSPHATE TO THE AZOKETONE PROCEEDS EXCEEDING CLEANLY, GIVING OFF NITROGEN GAS AS THE BY-PRODUCT. THE LAST STEP OF THIS HIGHLY EFFICIENT PROCESS IS THE CLEAVAGE OF THE PROTECTING GROUPS. TREATMENT OF THE T-BUTYL DIBENZYL PROTECTED DHAP WITH 10% TRIFLUOROACETIC ACID IN METHYLENE CHLORIDE AT ROOM TEMPERATURE SUCCESSFULLY CLEAVED THE PROTECTING GROUPS OVER A 4 HOUR PERIOD. THE ATTACHED NMR SPECTRA CLEARLY SHOW THAT THE T-BUTYL GROUP IS THE FIRST TO CLEAVE. THIS IS FOLLOWED BY THE SEQUENTIAL REMOVAL OF THE BENZYL GROUPS TO GIVE THE FIRST EXAMPLE OF THE SYNTHESIS OF [2-13C]DHAP. IN ADDITION, THE SMOOTH CLEAVAGE OF THE BENZYL PHOSPHATE GROUPS WITH TRIFLUOROACETIC ACID IS UNPRECEDENTED. THE NORMAL HYDROGENATION CLEAVAGE PROCEDURE IS INFERIOR BOTH BECAUSE OF THE LOW YIELDS AND THE LABOR-INTENSIVE WORKUP.
| Martinez, Rodolfo A; Glass, David R; Ortiz, Erick G et al. (2014) Synthesis of isotopically labeled 1,3-dithiane. J Labelled Comp Radiopharm 57:338-41 |
| Martinez, Rodolfo A; Glass, David R; Ortiz, Erick G et al. (2013) Large-scale preparation of (13) C-labeled 2-(phenylthio)acetic acid and the corresponding labeled sulfoxides and sulfones. J Labelled Comp Radiopharm 56:31-5 |
| Jenkins, Janelle E; Creager, Melinda S; Lewis, Randolph V et al. (2010) Quantitative Correlation between the protein primary sequences and secondary structures in spider dragline silks. Biomacromolecules 11:192-200 |
| Creager, Melinda S; Jenkins, Janelle E; Thagard-Yeaman, Leigh A et al. (2010) Solid-state NMR comparison of various spiders' dragline silk fiber. Biomacromolecules 11:2039-43 |
| Kim, Sun Hee; Aznar, Constantino; Brynda, Marcin et al. (2004) An EPR, ESEEM, structural NMR, and DFT study of a synthetic model for the covalently ring-linked tyrosine-histidine structure in the heme-copper oxidases. J Am Chem Soc 126:2328-38 |
| Ollivault-Shiflett, Morgane; Kimball, David B; Silks, L A Pete (2004) Synthesis of chiral 13C,77Se-labeled selones. J Org Chem 69:5150-2 |
| Schmidt, Bryan; Hillier, Warwick; McCracken, John et al. (2004) The use of stable isotopes and spectroscopy to investigate the energy transducing function of cytochrome c oxidase. Biochim Biophys Acta 1655:248-55 |
| Schmidt, Bryan; McCracken, John; Ferguson-Miller, Shelagh (2003) A discrete water exit pathway in the membrane protein cytochrome c oxidase. Proc Natl Acad Sci U S A 100:15539-42 |
| Gray, Chandele R; Sanz-Cervera, Juan F; Silks, Louis A et al. (2003) Studies on the biosynthesis of asperparaline A: origin of the spirosuccinimde ring system. J Am Chem Soc 125:14692-3 |
| Van Dien, Stephen J; Strovas, Tim; Lidstrom, Mary E (2003) Quantification of central metabolic fluxes in the facultative methylotroph methylobacterium extorquens AM1 using 13C-label tracing and mass spectrometry. Biotechnol Bioeng 84:45-55 |
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