Specifically labeled with isotopes

SUGARS SPECIFICALLY LABELED WITH ISOTOPES OF HYDROGEN ... 

IX. Tables of Known Sugars Specifically Labeled with Isotopes of Hydrogen.. 181... 

Most of the sugars specifically labeled with isotopes of hydrogen that have been synthesized were prepared for use in mechanistic studies of enzymes. 

Barker, S. A., and Bourne, E. J., Acetals and Ketals of the Tetritols, Pentitols and Hexitols, 7, 137-207 Barnett, J. E. G., Halogenated Carbohydrates, 22, 177-227 Barnett, J. E. G., and Corina, D. L., Sugars Specifically Labeled with Isotopes of Hydrogen, 27, 127-190 Barrett, Elliott P., Trends in the Development of Granular Adsorbents for Sugar Refining, 6, 205-230 Barry, C. P., and Honeyman, John, Fructose and Its Derivatives, 7, 53-98... 

Sometimes the strongly basic properties of Gngnard reagents can be turned to synthetic advantage A chemist needed samples of butane specifically labeled with deuterium the mass 2 isotope of hydrogen as shown... 

Hydrogen, isotopes of, sugars specifically labeled with,... 

The ratio of peak heights for HDS and H2S loss from 3, 3-d2- and 4, 4-d2-pentane thiols was found to differ in 12 eV El mass spectra compared with 70eV spectra [256]. An intramolecular isotope effect of 1.2 was observed in the loss of C3H7S2 in the El mass spectrum of bis-1, 3-dithiane specifically labelled with deuterium on one of the tertiary carbon atoms [762]. 

Intramolecular carbon isotope effects have been determined for the McLafferty rearrangement in metastable a-ethylbutyrophenone ions using molecules specifically labelled with 13C at either one of the [3 or at one of the 7 positions. The isotope effects /c2H4/fi3CCH obtained were 0.095 0.005 for the 7-13C compound and 1.017 0.d07 for the 3-13C compound [849]. 

Quantitative analysis has become possible due to technical advances in synthesis of complex molecules with isotopic labels at any one of many specific position and measurements of KIE determined accurately and precisely by mass-spectrometry and radioactive methods. The most informative method for elucidation of the enzyme reaction limiting step and nature of transition-state is the competitive labeled method (Schramm, 1999). This method is based on the use of two labeled preparations of the same substrate, one with the labeled atom at a site expected to experience bonding changes at the TS and a second preparation with a different labeled atom at a site remote from the bond-breaking site. Many molecules of interest can be specifically labeled with radioactive atoms T or I4C and can be incorporated into substrates that also contain stable isotopes D, 15N and 180. 

When the hydrogen transferred as hydride to the cofactor is retransferred to the same carbon atom in the product, the movement is far more difficult to detect. The conversion of D-glucose 6-phosphate (58) into lL-mt/o-inositol 1-phosphate (61) occurs by cyclization of the carbon skeleton, with formation of a new bond between C-l and C-6. When each carbon atom in turn was specifically labeled with tritium, there was complete retention of tritium, even in the presence of added NADH, although there was an apparent, small isotope-effect with D-glucose-5-t 6-phosphate.19 The mechanism proposed for the cyclization19 was an initial oxidation at C-5 to give NADH and xylo-hexos-5-ulose 6-phosphate (59), followed by an aldol reaction causing cyclization to lL-myo-inosose-2 1-phosphate (60), which is then... 

Labelling with Isotopic Hydrogen.—Various oestrogenic steroids with high specific radioactivity were obtained by reduction of their 2,4-dibromo- or 2,4-iodo-derivatives with tritium gas over 5% Pd-A Oa, to give 2,4-ditritiated products." Betamethasone 17-benzoate (484) was labelled [1,2- H2] by selective reduction of... 

II. Use of Stable Isotopes for Structure Elucidation - Mass spectrometry is commonly used in medicinal chemistry to determine the structure of therapeutic agents and their metabolites. The unequivocal interpretation of the mass spectrum for most classes of compounds requires the use of derivatives which are labeled specifically with stable isotopes. For example, the loss of 16 mass units from hydroxamic acids was shown to be due to the loss of the hydroxylamino oxygen by specific labeling with... 

Cappon. J.J.. Witters, K.D., Baart, J., Verdegem, P.J.E., Hoek, A.C., Luiten, R.J.H., Raap, J., and Lugtenburg. J., Synthesis of L-histidine specifically labelled with stable isotopes. Reel. Trav. Chim. Pays-Bas. 113, 318, 1994. 

This pathway to anhalonidine has now been shown to be essentially correct by in vivo experiments.33 Administration of [l,9-14C]peyoruvic acid (44) to peyote cacti resulted in an efficient and specific incorporation of activity into the alkaloid, without a change in isotopic ratio. The status of the amino-acid as a true intermediate was confirmed by chemical analysis to show that it is present in the peyote cactus. Further support for Scheme 5 was provided by incubation of [9-14C]peyoruvic acid (44) with fresh peyote slices. Carbon dioxide was evolved and on work-up the decarboxylation product was found to be the imine (45), specifically labelled with 14C at C(9). The production of the imine rather than the tetrahydroisoquinoline (43) suggests that the decarboxylation may be an oxidative process and this interesting reaction deserves further investigation. 

Isotopes are frequently used in attempts to correlate spectra with structure. For instance, substitution has been employed by a number of investigators (Pinchas et al, 1961 Becker et al, 1963 and Karabatsos, 1960). An example of its application is the synthesis by Howard and Miles (1964) of inosine specifically labeled with 0 as an aid in interpreting the band at 1673cm in inosine-6- 0. Spencer (1959) has used water containing 8.7 atom % excess of to investigate the mode of action of an arylsulfatase. (For details of these investigations, see Chapter 15.)... 

From the above discussion it is clear that it is of vital importance to gain easy access to carotenoids specifically labelled with stable isotopes, especially with C. In the next Section, the tools for synthesizing labelled carotenoids from simple starting materials will be discussed. The synthesis of labelled Cio-synthons suitable for preparing any carotenoid labelled in the central part at predetermined positions will be described. Next, the linear synthesis of the spheroidenes labelled with in the central part will be presented, followed by a new convergent synthetic scheme by which it is possible to label all carotenoids with isotopes in the central part of the molecule. 

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