3881-07-0Relevant articles and documents
Synthesis of aromatic 13C/2H-α-ketoacid precursors to be used in selective phenylalanine and tyrosine protein labelling
Lichtenecker, R. J.
, p. 7551 - 7560 (2015/01/08)
Recent progress in protein NMR spectroscopy revealed aromatic residues to be valuable information sources for performing structure and motion analysis of high molecular weight proteins. However, the applied NMR experiments require tailored isotope labelling patterns in order to regulate spin-relaxation pathways and optimize magnetization transfer. We introduced a methodology to use α-ketoacids as metabolic amino acid precursors in cell-based overexpression of phenylalanine and/or tyrosine labelled proteins in a recent publication, which we have now developed further by providing synthetic routes to access the corresponding side-chain labelled precursors. The target compounds allow for selective introduction of 13C-1H spin systems in a highly deuterated chemical environment and feature alternating 12C-13C-12C ring-patterns. The resulting isotope distribution is especially suited to render straightforward 13C spin relaxation experiments possible, which provide insight into the dynamic properties of the corresponding labelled proteins.
Synthesis of selectively 13C-labelled benzoic acid for nuclear magnetic resonance spectroscopic measurement of glycine conjugation activity
Akira,Hasegawa,Baba
, p. 845 - 853 (2007/10/02)
The synthesis of [4-13C]benzoic acid (BA) labelled in a single protonated carbon, for use as a probe to measure glycine conjugation activity by nuclear magnetic resonance (NMR) spectroscopy, has been reported. The labelled compound was prepared
An efficient synthesis of 1-[13C]-Bromobenzene
Geletneky,Balzer,Bock,Berger
, p. 503 - 507 (2007/10/02)
Various routes to functionalized benzenes labelled in position 1 were compared. 1-[13C]-Bromobenzene has been synthesized in 7 steps with an overall yield of 5.4% from [13C]-BaCO3, by optimizing the direct transformation o
Skeletal Rearrangements Preceding CO Loss from Metastable Phenoxymethylene Ions Derived from Phenoxyacetic Acid and Anisole
Molenaar-Langeveld, Tineke A.,Ingemann, Steen,Nibbering, Nico M. M.
, p. 1167 - 1178 (2007/10/02)
The loss of CHO2(.) from the molecular ion of phenoxyacetic acid and the expulsion of an H(.) atom from ionized anisole lead to phenoxymethylene ions, which fragment predominantly by CO loss on the microsecond time-scale.Carbon-13 labelling reveals that ca. 90percent of the CO molecules expelled from the metastable ions derived from phenoxyacetic acid incorporate the carbon atom from the 1-position of the phenyl group of the parent compound, whereas the residual CO molecules contain one of the other carbon atoms of the aromatic ring.The 2-fluoro- and 2-methylphenoxymethylene ions derived from the appropriate aryloxyacetic acids behave similarly, i.e. the carbon atom of the methylene group of the parent compound is not incorporated in the expelled CO molecules.In contrast, ca. 45percent of the CO molecules eliminated from the metastable phenoxymethylene ions formed from ionized anisole contain the carbon atom of the methyl group, while the remaining part contains the carbon atom from the 1-position of the phenyl ring of the parent compound.This result is taken as evidence for the occurrence of a skeletal rearrangement of the anisole molecular ion leading to an interchange between the carbon atom of the methyl group and the carbon atom at the 1-position of the ring.The elimination of CO from the metastable ions generated from either phenoxyacetic acid or anisole gives rise to a composite metastable peak.Conclusive evidence as to the formation of (+) isomers other than the phenoxymethylene ion is not obtained, indicating that the composite metastable peak is a result of two competing reactions both leading to CO loss.Possible mechanisms of these reactions are discussed together with the mechanism of the skeletal rearrangement of the molecular ion of anisole prior to H(.) loss.
Synthesis and NMR spectroscopy of stable isotope-labelled phenols and L-tyrosines
Winkel, C.,Aarts, M. W. M. M.,Heide, F. R. van der,Buitenhuis, E. G.,Lugtenburg, J.
, p. 139 - 146 (2007/10/02)
The syntheses of (17O)phenol from (17O)water, (18O)phenol from (18O)water, (1-13C)-phenol and (4-13C)phenol from (2-13C)acetone and (2-13C)phenol and (3-13C)phenol from (1-13C)acetone with high isotopic enrichment are described.The labelled phenols are converted into their corresponding L-tyrosines by the bacterium Erwinia herbicola.A full analysis of the 1H and 13C NMR spectra of phenol and L-tyrosine is reported.
An Efficient Chemomicrobiological Synthesis of Stable Isotope-Labeled L-Tyrosine and L-Phenylalanine
Walker, T. E.,Matheny, C.,Storm, C. B.,Hayden, H.
, p. 1175 - 1179 (2007/10/02)
L-Tyrosine specifically labeled with 2H, 13C, 18O, or 15N has been synthesized by using a combination of organic synthetic methods and the β-tyrosinase enzyme activity of the bacterium Erwinia herbicola.The following L-tyrosine isotopomers were prepared: L-tyrosine from phenol and L-serine, L-tyrosine from phenol and L-serine, L-tyrosine from phenol and L-serine, L-tyrosine from ammonium sulfate, phenol, and pyruvate, and L-tyrosine from phenol and L-serine.The β-tyrosinase activitywas also used to prepare 2'-fluoro-L-tyrosine and 3'-fluoro-L-tyrosine from 3-fluorophenol and 2-fluorophenol, respectively.Phenol enriched with 13C was prepared by the condensation of acetone with nitromalonaldehyde, reduction of the resulting p-nitrophenol to p-aminophenol, and reductive removal of the nitrogen from the diazonium salt to form either - or phenol in a 40percent overall yield from acetone.The yields of L-tyrosine were typically around 90percent from labeled phenol.Labeled L-phenylalanine was chemically prepared from L-tyrosine in a 75percent overall yield.This was deemed the best approach to labeled L-phenylalanine, given the efficient method for preparing L-tyrosine from phenol.The approach to labeled L-phenylalanine represents a unique combination of chemical synthesis (phenol), biosynthesis (L-tyrosine), and finally chemical synthesis (L-phenylalanine).The chirality is introduced by the biochemical step, obviating the need for elaborate and inherently inefficient chiral manipulations.
