C-Labeling

C- (112, 113), 4- C- and 5- C-thiazoles (112) were prepared by the same general pathway from the corresponding " C-labeled 2-aminothiazoles synthesized by the Hantzsch cyclization of C-thiourea, l- C-2-bromoethanal, and 2- C-2-bromoethanal, respectively (112). A mixture of 4- and 5- C-thiazoles was prepared by the same general... 

FIGURE 26 8 The distribu tion of the C label in citronellal biosynthesized from acetate in which the methyl carbon was isoto pically enriched with C... 

AIBN was synthesized using C-labeled reagents and the tagged compound was used to initiate polymerization of methyl methacrylate and styrene. 

The mode of action has not yet been elucidated but the manufacturer states that it probably behaves like the herbicide triflurolin and its congeners. These materials inhibit cell division by binding to tubuHn thereby internipting micro-tubule development. This, in turn, stops spindle fiber formation essential to mitosis and cell division. Experiments with C-labeled Prime+ show that it is acutely toxic to fish with estimated LC q (96 h) of less than 100 ppb for rainbow trout and bluegiU. sunfish. However, channel catfish did not exhibit any toxic response at the maximum attainable water concentration (10). 

Even higher organisms can be used for the production of labeled compounds. Plants, tobacco, or Canna indica for example, when grown in an exclusive atmosphere of radioactive carbon dioxide, [ 002], utilize the labeled precursor as the sole source of carbon for photosynthesis. After a suitable period of growth, almost every carbon atom in the plant is radioactive. Thus, plants can serve as an available source of C-labeled carbohydrates (9). 

Application of NMR spectroscopy to heterocyclic chemistry has developed very rapidly during the past 15 years, and the technique is now used almost as routinely as H NMR spectroscopy. There are four main areas of application of interest to the heterocyclic chemist (i) elucidation of structure, where the method can be particularly valuable for complex natural products such as alkaloids and carbohydrate antibiotics (ii) stereochemical studies, especially conformational analysis of saturated heterocyclic systems (iii) the correlation of various theoretical aspects of structure and electronic distribution with chemical shifts, coupling constants and other NMR derived parameters and (iv) the unravelling of biosynthetic pathways to natural products, where, in contrast to related studies with " C-labelled precursors, stepwise degradation of the secondary metabolite is usually unnecessary. 

Hoffmann and Schiittler showed by C labelling (75CB844) that (81) generated by chelotropic extrusion from a bicycloheptadiene derivative did not isomerize to oxirene. This is as expected from MO calculations (Section 5.05.6.2). 

An elegant NMR experiment by the group of Lynn Jelinski at Cornell University has established that at least part of the microcrystals is built up from the polyalanine repeats in the protein chains. These experiments, which were made on C-enriched proteins produced by feeding the spiders C-labeled alanine, showed that there were two populations of alanine side chains, one ordered and oriented perpendicular to the fiber axis and a second less ordered. Jelinski s interpretation is that parts of the polyalanine sequences are incorporated as p strands in the microcrystals with an orientation parallel to the fiber axis. Whether or not the Gly-Gly-X repeats also form P strands in the microcrystals remains an open question. 

Although nucleophilic aromatic substitution by the elimination-addition mechanism is most commonly seen with very strong amide bases, it also occurs with bases such as hydroxide ion at high temperatures. A " C-labeling study revealed that hydrolysis of chlorobenzene proceeds by way of a benzyne intennediate. 

On the other hand, " C-labeling studies have shown that the base-promoted hydrolysis of chlorobenzene (second entry in Table 24.3) proceeds by the elimination-addition mechanism and involves benzyne as an intermediate. 

Definitive identification of lysine as the modified active-site residue has come from radioisotope-labeling studies. NaBH4 reduction of the aldolase Schiff base intermediate formed from C-labeled dihydroxyacetone-P yields an enzyme covalently labeled with C. Acid hydrolysis of the inactivated enzyme liberates a novel C-labeled amino acid, N -dihydroxypropyl-L-lysine. This is the product anticipated from reduction of the Schiff base formed between a lysine residue and the C-labeled dihydroxy-acetone-P. (The phosphate group is lost during acid hydrolysis of the inactivated enzyme.) The use of C labeling in a case such as this facilitates the separation and identification of the telltale amino acid. 

C-labeled carbon dioxide is administered to a green plant, and shortly thereafter the following compounds are isolated from the plant 3-phosphoglycerate, glucose, erythrose-4-phosphate, sedoheptulose-l,7-bisphosphate, ribose-5-phosphate. In which carbon atoms will radioactivity be found ... 

Even though acetate units, such as those obtained from fatty acid oxidation, cannot be used for net synthesis of carbohydrate in animals, labeled carbon from " C-labeled acetate can be found in newly synthesized glucose (for example, in liver glycogen) in animal tracer studies. Explain how this can be. Which carbons of glucose would you expect to be the first to be labeled by "Relabeled acetate ... 

Independent synthesis of IQ, eliminating the alkylating reaction step, involved the cyclizations of 7-R-5-amino-6-methylaminoquinolines with cyanogen bromide. When " C-labeled BrCN was used, the corresponding 2- " C-labeled analogues of IQ and MelQ were synthesized (83ACSI57). The diamines are available from 5-nitroderivatives, which in turn have been prepared by nitration of methylami-noderivatives (82CPB1857). 

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