Kuhn-Roth degradation

Kuhn-Roth degradation of the radioactive pteroside should have a specific activity one-ninth of that of the precursor MVA. In the event the ratio was 1.41 9. The authors claim that since this type of degradation of an aromatic methyl is inefficient this evidence supports their scheme, although there may be other interpretations of these data. 

The biosynthesis of the cyclopropyl ring was studied further with propionate doubly labeled with both deuterium and carbon-13 (CD3CH2 C02Na) (52). The results showed that the propionate unit was incorporated intact, but with low efficiency, apparendy because of deuterium-related kinetic effects that accompany an unexpect modification of propionate during incorporation. The stereochemical subdeties were probed by Kuhn-Roth degradation of the labeled natural product, conversion of the cyclopropanecarboxylate thus produced into cyclopropyl phenyl carbinol, and resolution of (15)-camphanate esters— a risky undertaking that was... 

Kuhn-Roth C-Methyl Determination, Kuhn-Roth Degradation, Kuhn-Roth Determination)... 

This reaction was first reported by Kuhn and Roth in 1933. It is a method for quantifying the number of methyl groups attached to the carbon atom in an organic molecule, which involves the oxidation of such an organic compound with chromic acid in the presence of sulfuric acid, followed by steam distillation to collect the generated acetic acid and quantification of the acetic acid via acid/base titration. In addition, the collected acetic acid can be further analyzed by conversion of acetic acid into lithium acetate, pyrolysis of lithium acetate to acetone, and transformation of acetone into iodoform by hypoiodite. Therefore, this reaction is generally known as the Kuhn-Roth C-methyl determination, Kuhn-Roth chromic acid oxidation, Kuhn-Roth degradation, Kuhn-Roth determination, or Kuhn-Roth oxidation. " ... 

Hofmann degradation of desbase A gives three products (79)2 one produced by a methoxylating fission, to which structure LXXI is ascribed, and two produced by D-type fission, didesbase AD, mp 73° (LXXII) and didesbase AD, mp 113° (LXXIII). Both these bases give the same tetrahydro derivative, hence they differ only in the position of the double bond. That V-type fission has not occurred is clear from the Kuhn-Roth oxidation of the tetrahydro derivative, which still shows the presence of only one G -methyl. 

The incorporation of [2-14C]pyruvate and [l-14C]acetate into sugars 17 and 18 was investigated.27 Oxidation of the methyl glycosides of sugar 17 with periodate yielded acetaldehyde from the 1-hydroxyethyl branch. The acetaldehyde (2,4-dinitrophenyl)hydrazone was further oxidized by Kuhn-Roth oxidation to acetic acid, which was degraded by the Schmidt reaction to methylamine and carbon dioxide. Periodate oxidation of the methyl glycosides of sugar 18 produced acetic acid from the C-acetyl branch. The acetic acid was isolated, and purified as 1-acetamidonaphthalene. 

Further structural information was obtained through degradation and other chemical studies. Modified Kuhn-Roth oxidation of selagine gave... 

The structure of nobiline was largely inferred from data derived from mass spectra, NMR- and IR-spectra, and confirmed in specific instances by crucial chemical experiments. A six-membered ketone and a y-lactone account for the three oxygens. A Kuhn-Roth oxidation confirmed the presence of two C-methyls and the elimination of trimethylamine in the first stage of the Hofmann degradation confirmed the extracyclic dimethylamino group. These and other data could best be interpreted by two structures the preferred one being XXVI 75, 76). 

Lanosterol prepared from the labeled squalene mixture, was degraded to acetate by Kuhn-Roth oxidation (sulfochromic treatment) and in turn, the acetate was degraded to ethylene for mass spectrometric analysis. Consideration of the labeling patterns reveals that only structure D can give rise to ethylene containing at both carbon atoms. Since such doubly labeled ethylene was actually detected, it was concluded that the process of two 1,2-methyl migrations actually occurs. 

The specific activities of labeled variotin and its degradation products were compared to establish the distribution of in the molecule of variotin. The degradation is illustrated in Fig. 2. Acetic acid was obtained from Qg-hydroxy acid and 3-methylsuberic acid by Kuhn-Roth oxidation. Each product was identified by infrared absorption spectrum. 

Incorporations of p- C-tryptophan (29a) and p- C-tryptophan (29b) quickly established that this amino acid is the biological precursor to the C and D rings (41). Kuhn-Roth oxidation of labeled (1) derived from (29 a), followed by Schmidt degradation of the resulting acetic acid, located all of the radioaetivity at C-3 of (1). This result was later confirmed by NMR analysis of streptonigrin derived from (29b). Other experiments showed that while methionine had labeled the four methyls of (1) equally, C-3 of serine — the major precursor to the biological one-carbon pool — labeled the three 0-methyls almost exclusively (41). 

In order to determine the isotope distribution after feeding experiments with radioactive precursors, the chemical degradation reactions, summarized in Fig. 4 (structures 62-65), were used. The carbon atoms C(6) and C(11) could be analyzed easily for measurement of radioactivity by Kuhn-Roth oxidation. They were, therefore, preferentially selected as labeled sites. 

In experiment 1 (Table VII), the precursors emodin (76) and emodin-anthrone (77) were labeled with the same isotope ( " C) in two different positions [at C(3) and C(ll)] by the synthetic procedures described above. After incorporation, the corresponding carbon atoms of the ergochrome EE (2) could be analyzed as acetic acid by Kuhn-Roth oxidation. The specific incorporations were derived from the activities of the two carbon atoms, determined separately by Schmidt degradation of the acetic acid. The results show that emodinanthrone (77) is incorporated into ergochrome EE (2) 4.5 times more effectively than emodin (76). 

On treatment with periodate, the third ozonolysis product, 3-methyloctane-l,7,8-triol(32), yielded formaldehyde [(21)] and 5-methyl-7-hydroxyheptanal (33). The hydroxyaldehyde 33 was oxidized by chromium trioxide to 3-methylpimelic acid (34). Schmidt degradation of the latter gave carbon dioxide [C(14) and C(20)] and l,5-diamino-2-methylpentane (35) (isolated as dipicrate). Kuhn-Roth oxidation of octanetriol (32) yielded one equivalent of acetic acid [C(16) and 16-methyl]. 

Schmidt degradation of the acid 44 and fixation of the evolved carbon dioxide with barium hydroxide localized the label at C(17). Kuhn-Roth oxidation of 44 and Schmidt cleavage of the resulting two equivalents of acetic acid yielded the activities of both C(16) and its methyl substituent by comparison of the same sequence on the deacetylated y-lactams 39 and 40, respectively. Ozonolysis of acid 44 followed by reduction gave the epimeric lactam triols 45a and 45b, respectively. The usual Kuhn-Roth and Schmidt route offered independent determinations of C(ll) and C(5). A combined value for C(14) and C(15) could be calculated from the activity... 

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