Amino acids, deuteration

The signals in the spectra of the partially deuterated amino acid (Figs. 1.2 b-d and 1.2 f)... 

These results demonstrate that incubation of isolated cells with deuterated precursors provides a means of elucidating neurotransmitter biosynthetic pathways. A range of deuterated precursors, including deuterated amino acids, could be produced for more extensive studies. 

The application of the photo-CIDNP method in conjunction with the introduction of deuterated amino acids holds great promise for the study of protein-protein and protein-nucleic acid interactions with NMR. In this contribution it has been shown that this allows partial assignment of the aromatic part of the protein spectrum in a convenient way. Binding of DNA fragments affects both the resonances of the phenylalanyl residues as well as the resonances of the tyrosines at the surface of the protein. The disappearance of the emission signals of the latter provides direct evidence for their Involvement in the interaction with DNA. 

Another advantage of this approach is the possibility of preparing stereo-specifically a series (by varying the R group of the keto acid precursor at will) of a-deuterated amino acids by simply undertaking the chemical reduction in heavy water. 

The success of this approach is helpful for the preparation of specific j8-deuterated amino acids. The following transformation is an outline of the method for racemizing the a-carbon center of iV-benzoylphenylalanine via an oxazoline intermediate. The two diastereoisomers can be separated by conventional means. 

An extension of site-directed spin labeling is to monitor H-ESEEM from a deuterated amino acid (valine or leucine) that is introduced at a fixed position, i, in the peptide sequence. The nitroxide spin label is then attached at a cysteine residue that is stepped sj tematically away from the deuterated residue. For an a-helical peptide, H-ESEEM is observed when the spin label is at position z- -3, i.e., in register with the deuterated residue, but not at position i + 2. For a (Tsheet peptide, on the other hand, H-ESEEM is observed when the spin label is at position i -I- 2 on the same side of the p-sheet as the deuterated residue, but not at position i -I- 3 on the opposite side of the p-sheet. Therefore the H-ESEEM amplitude, which is inversely proportional to the sixth power of the distance between electron and nuclear spins, directly reflects the characteristic periodicity of the peptide secondary structure, in the vicinity of the deuterated residue. 

Katritzky et al.508 have measured rates of deuteration of aminopyridine by deuterated sulphuric acid (Table 146), and for the 4-amino and 2-amino-5-methyl compounds, the general increase in rate with increasing acidity, dlogkjd (—H0) 0.6, shows reaction to be occurring on the conjugate acids. For the latter compound this is only true at acidities > —H0 = 4.0, below which rates are relatively independent of acidity indicating reaction on the free base. For the 2,6-dichloro... 

Finally, Katritzky et al.sii have measured first-order rate coefficients for deuteration of pyrimidines by deuterated sulphuric acid (Table 152), and all pD and —D0 values given in the Table refer, as in the earlier work, to a temperature of 20 °C. For 2-aminopyrimidine, reaction clearly occurs on the free base and comparison of the data with the earlier work on anilines and by making a number of assumptions, conjugate acid at higher acidities is apparent and this follows the previously established pattern. This work yielded a value of 0.55 for [Pg.236]

With this background, the finding by Merck chemists [51] that unprotected dehydro / -amino acids are good substrates for the Rh-catalyzed hydrogenations was both very unexpected and very exciting. Interestingly, deuteration experiments indicate that it is not the enamine C=C bond which is reduced but the tautomeric imine Not only simple derivatives but also the complex intermediate for MK-0431 (see Fig. 37.10) can be hydrogenated successfully, and the latter has been pro-... 

Mitulovic et al. [Ill] presented a procedure for the preparation of a-carbon deuterium-labelled a-amino acids from native amino acids via a Schiff-base racem-ization protocol in deuterated acetic acid involving a preparative chromatography step of the obtained Z-protected deuterium-labeled amino acid derivatives on the tBuCQN-CSP [ill]. The analytical control of the enantiomeric products after DNP, Z, or DNZ derivatization showed a high enantiomeric excess (97-98%) and also a high isotopic purity (99%) by MS. 

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