13 Carbon-labelling

Sections I-V of this chapter deal with the syntheses of unsaturated organic compounds playing an essential role in biochemical processes of life. Numerous polyunsaturated compounds have been synthesized in order to elucidate their physiological role, for instance in brain. However, the main impact on permanent searches for new improved methods of synthesis of isotopically labelled dienes and polyenes comes from nuclear medicine and nuclear pharmacy. The deuterium and carbon-13 labelled polyunsaturated compounds are needed as internal standards in mass spectral determinations of very low concentrations of biologically active substances in biological fluids. 

Quantification is usually achieved by a standard addition method, use of labeled internal standards, and/or external calibration curves. In order to allow for matrix interferences the most reliable method for a correct quantitation of the analytes is the isotope dilution method, which takes into account intrinsic matrix responses, using a deuterated internal standard or carbon-13-labeled internal standard with the same chemistry as the pesticide being analyzed (i.e., d-5 atrazine for atrazine analysis). Quality analytical parameters are usually achieved by participation in interlaboratory exercises and/or the analysis of certified reference materials [21]. 

Serianni, A.S., Nunez, H.A. and Barker, R., Cyanohydrin synthesis studies with carbon-13-labeled cyanide. 7. Org. Chem., 1980, 45, 3329. 

In Figure 7, the labelled internal standards used for the quantification of eight selected key sesame odorants identified on the basis of AEDA results [46, 52] are shown. Most of them were labelled with deuterium since their preparation was relatively inexpensive. In the case of 4-hydroxy-2,5-dimethyl-3(2H)-furanone, the labelling had to be performed via the more expensive carbon-13 labelled intermediates [68], since the deuterated standard underwent significant protium-deuterium exchanges (unpublished data). 

Figure 7. Labelled internal standards used for the quantification of key sesame odorants. deuterium label, carbon-13-label.

Flash vacuum thermolysis of the formal Diels-Alder adduct (10) of acetyl-methyloxirene to tetramethyl-l,2,4,5-benzenetetracarboxylate to give acetyl-methylketene (15, in Scheme 1) was examined in an attempt to find an example of nonstatistical dynamics effect on product distribution.29 With two carbon-13-labeled starting materials ( and show the labeled carbon in separated experiments), the reaction yielded 15 with different 13C locations. It was originally expected that 10 would give 12, which then via carbene formation would yield 15a and 15b. The ratio of the two products was anticipated to show the occurrence of nonstatistical product distributions. Compound 15c might be formed via 12 and 13, but this route was considered to be minor since 13 was much unstable than 14. 

The syntheses of carbon-13 labelled trans-tricyclic ketones 93 and 94 have been carried out79 via the cyanidation reaction of organoborane (equation 43). The isomerically pure tram -tricyclic ketones 93 and 94 were needed in connection with the undertaken synthesis... 

V. H. Kollman, J. L. Hanners, J. Y. Hutson, T. W. Whaley, D. G. Ott, and C. T. Gregg, Large scale photosynthetic production of carbon-13 labeled sugars The tobacco leaf system, Biochem. Biophys. Res. Comm., 50 (1973) 826-831. 

Hatcher PG, Bortiatynski JM, Minard RD et al (1993) Use of high-resolution carbon-13 NMR to examine the enzymatic covalent binding of carbon-13-labeled 2, 4-dichlorophenol to humic substances. Environ Sci Technol 27 2096-2103... 

McNamara, K. M. and Gleason, K. K. (1993), Comparison of tantalum and rhenium filaments in diamond CVD using selective carbon-13 labeling. J. Electrochem. Soc., 140(2) L22-L24. 

Naikwadi KP, Karasek FW (1990), Intern. J. Environ. Anal. Chem. 38 329-342. Use of carbon-13 labelled dioxin mixture for analysis of polychlorinated dibenzo-p-dioxins in environmental samples by GC/MS11... 

Zahn, T.J., Ksebati, M., and Gibbs, R.A. (1998). Synthesis and conformational analysis of Bis-carbon-13 labeled farnesyl diphosphate analogs. Tetrahedron Lett 39 3991-3994. 

Deuterium and carbon-13 labelled cationic hexafluoroantimonate complexes in a study of the catalytic carbonylation of methanol to acetic acid... 

The reaction is facile for manganese but requires elevated temperatures for rhenium. Carbon-13 labeling experiments using [Mn(CO)4(COPh)(COMe)] demonstrate that while methyl migration is preferred to phenyl migration, an elimination step from the intermediate [Mn(CO)4(Ph)(COMe)] occurs more readily. 

Simultaneous measurements of plasma levels of deuterated and unlabeled d- and 1-propoxyphene revealed that the plasma levels of the more analge-sically active d-isomer were higher and the half-life was longer. On the other hand, simultaneous measurements of (+)- and (-)-propranolol indicated no differences in the rate of elimination of the isomers in dogs. Finally, the metabolism of carbon-13 labeled R- and S-a -methyldopa has revealed a high degree of stereoselectivity favoring the S-enantiomer for both transport across the blood-brain barrier and brain decarboxylase activity 7... 

Based on the data obtained (Figure 8) from the control experiments A and B, which only showed the unlabeled (m/z 118) or the fully labeled 2-oxopropanol (m/z 121), the two isotopomers obtained from mixture C clearly indicated that no isotope scrambling had occurred (the fragments at m/z 119 and m/z 120 are caused by M+1 or M-I fragments of m/z 118 or m/z 121, respectively). Thus, the data confirmed that the 2-oxopropanol present in the reaction system is exclusively formed as a carbon-3 modul from either glucose or the carbon-13 labeled glucose, respectively. 

Hammerschmidt, E, Kahlig, H., and Muller, N., Biosynthesis of natural products with a P-C bond. Part 6. Preparation of deuterium- and carbon-13-labelled L-alanyl- and L-alanyl-L-alanyl-(2-aminoet-hyl)phosphonic acids and their use in biosynthetic studies of fosfomycin in Streptomyces fradiae, J. Chem. Soc., Perkin Trans. 1, 365, 1991. 

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