Labeling studies

Although nucleophilic aromatic substitution by the elimination-addition mecha nism IS most commonly seen with very strong amide bases it also occurs with bases such as hydroxide ion at high temperatures A labeling study revealed that hydroly SIS of chlorobenzene proceeds by way of a benzyne intermediate... 

On the other hand labeling studies have shown that the base promoted hydro lysis of chlorobenzene (second entry m Table 24 3) proceeds by the elimination-addition mechanism and involves benzyne as an intermediate... 

Similarly, anthranHic acid (28) has been suggested as a reasonable precursor and some eady labeling studies have been carried out showing that dictamnine [484-29-7] (135), C22H2NO2, from Dictamnus albus and skimminanine [83-95-4] (136), C24H23NO4, from Skimmiajaponica incorporate anthranHic acid in a nonrandom fashion (96,97). 

The iacrease ia reactivity of coordinated N2 has been assumed to be associated with iacreased bond length and decreased stretching frequency. A labeling study has shown that this is an oversimplification. In the protonolysis of [Cp 22 (N2)]2 2 hydraziae produced comes equally from terminal and bridging N2. An iatermediate, such as [86165-22-2] was proposed where the bridging and terminal N2 have become equivalent. 

Mechanistic studies (6,26,27,67) have shown that the acyl enzyme species is the ring opened compound (13), which can tautomerize to the transientiy inhibited amino acrylate (14), and both of these species can react further to give irreversibly inactivated enzyme. Three inactivated forms of the enzyme have been detected. Two, according to labeling studies, retain the complete clavulanate skeleton and the other retains only the carbon chain of the P-lactam ring. Stmcture (15) has been suggested as one possible inactivated form. 

For fV-methylpyrazoIe (99), the molecular ion of which is less intense than pyrazole (a common feature for methyl-substituted pyrazoles (67ZOR1540)), the fragmentation pattern involves the methyl group (Scheme 2). These results were established using H, C and N labelling studies. 

At least three distinct mechanisms can be written for these reactions. Write down some possible mechanisms, and suggest isotopic labeling studies that could distinguish among the possibilities you have proposed. 

Other mechanisms must also operate, however, to account tor the fact that 5-10% of the product is formed with retained configuration at the chiral center. Isotopic labeling studies have also demonstrated that the 3-bromo-2-butyl radical undergoes reversible loss of bromine atom to give 2-butene at a rate which is competitive with that of the bromination reaction ... 

A deuterium labeling study has been performed with the results shown. Discuss the details of the mechanism that are revealed by these results. Is there a feasible mechanism that would have led to B having an alternative label distribution ... 

Labeling studies have shown that the 3-ketone provides the carboxyl group of (28). This led to the conclusion that attack of hydroxide ion occurs at C-3 to give (30), and subsequently the norsteroid (32) via the transition state (31). Attack at C-3 to give adduct (30) is favored over attack at C-4... 

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. 

Wasserman demonstrated with 0 labeling studies that the amide carbonyl oxygen is incorporated into the oxazole ring upon cyclization... 

The mechanism shown in Figure 21.7 is supported by isotope-labeling studies. When ethyl propanoate labeled with lsO in the ether-like oxygen is hydrolyzed in aqueous NaOH, the l80 label shows up exclusively in the ethanol product. None of the label remains with the propanoic acid, indicating that saponification occurs by cleavage of the C-OR bond rather than the CO—R bond. 

A study of the chlorine oxidation of 2-hydroxyethyl octyl sulphoxide92 (equation 28) showed that a cyclic intermediate is probably involved in the process which gives the sulphone in good yield. Labelling studies have shown that the hydroxyl group is replaced by a chlorine atom whilst the hydroxyl oxygen atom is transferred to the sulphur atom. A similar result was obtained for 3-hydroxypropyl and 4-hydroxybutyl alkyl sulphoxides93. 

J Clin Psychopharmacol 23 294-304, 2003a Kranzler HR, Pierucci-Lagha A, Feinn R, et al Effects of ondansetron in early- vs late-onset alcoholics a prospective, open-label study. Alcohol Clin Exp Res 27 1150-1155, 2003b... 

While none of these neutrophil receptors has yet been sequenced, partial purification of the formyl peptide receptors has been reported (16). The formyl peptide receptor is particularly attractive because of the extensive structure-activity studies on peptide ligands by Freer and coworkers (17,18). The receptor is a trans-membrane glycoprotein with apparent molecular weight of 60,000 based on proteolysis (19) and photoaffinity (20) labeling studies. 

Evidence for migration of the arylthio group across the double bond comes from C-14 labeling studies on ester 213 and product studies from unsymmetrical vinyl sulfonates 214 (181). Complete scrambling of the C-14... 

A comparison of the structures of penicillin and Dalanyl-Dalanine (cf. structures 41 and 42) shows that there is a great deal of similarity between the two molecules. Penicillin is essentially an acylated cyclic dipeptide of Dcysteine and Dvaline (84). As such, it contains a peptide bond, that of the /3-lactam ring, that can acylate the enzyme. Labeling studies of the peptidoglycan transpeptidase of Bacillus subtilis indicate that radioactive penicillin reacts with a sulfhydryl group of a cysteine residue of the enzyme (86). 

Gorbakov W, Kim H, Gronsky B, Lang W (2005) HCV RNA results from a Phase II, randomized, open-labeled study of omega interferon (IFN) with or without ribavirin in IFN-naive genotype 1 chronic HCV patients. Hepatology 42 705A... 

The chemical reactivity of the organoruthenium and -osmium porphyrin complexes varies considerably, with some complexes (M(Por)R2, M(Por)R and Os(OEP)(NO)R) at least moderately air stable, while most are light sensitive and Stability is improved by handling them in the dark. Chemical transformations directly involving the methyl group have been observed for Ru(TTP) NO)Me, which inserts SO2 to form Ru(TTP)(N0) 0S(0)Me and Ru(OEP)Me which undergoes H- atom abstraction reactions with the radical trap TEMPO in benzene solution to yield Ru(OEP)(CO)(TEMPO). Isotope labeling studies indicate that the carbonyl carbon atom is derived from the methyl carbon atom. "" Reaction of... 

The anomeric configuration is set in the reductive lithiation step, which proceeds via a radical intermediate. Hyperconjugative stabilization favors axial disposition of the intermediate radical, which after another single electron reduction leads to a configurationally stable a-alkoxylithium intermediate. Protonation thus provides the j9-anomer. The authors were unable to determine the stereoselectivity of the alkylation step, due to difficulty with isolation. However, deuterium labeling studies pointed to the intervention of an equatorially disposed a-alkoxylithium 7 (thermodynamically favored due to the reverse anomeric effect) which undergoes alkylation with retention of configuration (Eq. 2). 

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