Phenylalanine deuterated

In the solid, dynamics occurring within the kHz frequency scale can be examined by line-shape analysis of 2H or 13C (or 15N) NMR spectra by respective quadrupolar and CSA interactions, isotropic peaks16,59-62 or dipolar couplings based on dipolar chemical shift correlation experiments.63-65 In the former, tyrosine or phenylalanine dynamics of Leu-enkephalin are examined at frequencies of 103-104 Hz by 2H NMR of deuterated samples and at 1.3 x 102 Hz by 13C CPMAS, respectively.60-62 In the latter, dipolar interactions between the 1H-1H and 1H-13C (or 3H-15N) pairs are determined by a 2D-MAS SLF technique such as wide-line separation (WISE)63 and dipolar chemical shift separation (DIP-SHIFT)64,65 or Lee-Goldburg CP (LGCP) NMR,66 respectively. In the WISE experiment, the XH wide-line spectrum of the blend polymers consists of a rather featureless superposition of components with different dipolar widths which can be separated in the second frequency dimension and related to structural units according to their 13C chemical shifts.63... 

Remarkable success has been achieved by Fryzuk and Bosnich (247) using the complex [Rh(5,5-chiraphos)(COD)]+, where the chiral ligand 25,55-bis(diphenylphosphino)butane, a diphosphine chiral at carbons (25), is readily synthesized from 2R,3R-butane diol. TheZ-isomers of the prochiral a-N-acylaminoacrylic acid substrates were hydrogenated at ambient conditions to / -products with very high enantiomeric excess indeed, leucine and phenylalanine derivatives were obtained in complete optical purity. Catalytic deuteration was shown to lead to pure chiral f3-carbon centers as well as a-carbon centers in the leucine and phenylal-... 

Although DIOS-MS is mainly a tool for qualitative analysis, many examples have shown that quantitative analysis is possible when internal standards are used. These may either be isotope-labelled - mostly deuterated - compounds or structurally related analogues. For example, subsequent to electrospray deposition, amino acids such as phenylalanine and tyrosine have been successfully quantified by means of DIOS-MS using their deuterated analogues as internal standards. 

An intramolecular hydrogen migration observed in the hydroxylation of aromatic rings in certain enzyme-catalyzed reactions as well as some chemical reactions. The rearrangement was first observed at the National Institutes of Health (hence the name NIH ) in studies of the synthesis of L-tyrosine from L-phenylalanine via phenylalanine hydroxylase. Observation of this shift requires appropriate deuteration of the aromatic reactant. 

Reduction of (S)-pinanediol [phenyl(chloro)methyl]boronate with commercially available lithium triethylborodeuteride yields a chirally deuterated benzylboronic ester. Deboronation of the deuterated benzylboronic ester with hydrogen peroxide yields chirally deuterated benzyl alcohol in 96-98% ee70. The conversion of the deuterated benzylboronic ester to chirally deuterated phenylalanine has also been accomplished (Section 1.1.2.1.4.2.). 

Boronic ester homologation has been used to synthesize specifically deuterated phenylalanine by the pathway shown in Figure B6.3. 

PF Fitzpatrick. Kinetic isotope effects on hydroxylation of ring-deuterated phenylalanines by tyrosine hydroxylase provide evidence against partitioning of an arene oxide intermediate. J Am Chem Soc 116 1133—1134, 1994. 

Fig. 8. EPR spectra of in cyanobateria (Met-27 mutant Anabaena variabilis) grown in a medium supplemented with 90 pM protonated methionine (A) 90 pM deuterated methionine (B) and wild-type Synechocystis-6802 cells grown in medium containing 0.5 mM phenylalanine, 0.25 mM tryptophan and 0.25 mM perdeuterated tyrosine (C). All spectra were recorded 2 min after illumination. The three signals were measured at a gain of 3.2, 3.2 and 5, respectively. Figure source Barry and Babcock (1987) Tyrosine radicals are involved in the photosynthetic oxygen-evolving system. Proc Nat Acad Sci, USA 84 7100.

Phenylalanine ammonia-lyase was shown to have a stepwise mechanism with a carbanion intermediate by measurement of N isotope effects with deuterated and unlabeled dihydrophenylalanine, a slow alternate substrate (99). This was a particularly intriguing case because the study was undertaken because it was thought that the mechanism would not be a carbanion one. 

Culbertson, C. T. and Jorgenson, J. W., Separation of fluorescently derivatized deuterated isotopomers of phenylalanine using micellar electrokinetic chromatography and flow counterbalanced micellar tltctxd aaticchmrasLtogxsLph.y. Journal of Microcolumn Separations 1999, 11,175-183. 

Zaylak M, -J., Curtius H-Ch, Leimbacher W., and Redweik U (1977) Quantitation of deuterated and non-deuterated phenylalanine and tyrosine in human plasma using the selective ion monitoring method with combined gas chromatography-mass spectrometry. Application to the m vivo measurement of phenylalanime-4-monooxygenase activity. / Chromatogr 142, 523-531... 

Figure 2. The aromatic part of the 360 MHz proton NHR spectrum of gene-5 protein, recorded at 37 (A) with normal phenylalanines (B) with deuterated phenylalanines.

Leimbacher, W., and Redweik, U. Quantitation of Deuterated and Non-deuterated Phenylalanine and Tyrosine in Human Plasma Using the Selected Ion Monitoring Method with Combined Gas Chromatography-Mass Spectrometry. Application to the In Vivo Measurement of Phenyla1anine-4-monooxygenas e Activity... 

A simple extension of the foregoing synthesis was also shown to be usefrd for making phenylalanine asymmetrically deuterated in the CHD group [68], Azido substituted boronic esters have been mentioned in passing in Section 8.3.5 in conjunction with another synthesis (Scheme 8.22) [54]. 

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