Synthesi of labelled compounds

Various other radiation-induced reactions have been studied for potential use in the industry on a pilot-plant scale. Among these may be mentioned hydrocarbon cracking (i.e., production of lower-molecular-weight hydrocarbons from higher-molecular-weight material), isomerization of organic molecules, and synthesis of labeled compounds with radioactive nuclei. When organic compounds are irradiated in the pure state or in aqueous solution, dimeric... 

Chemical synthesis of labeled compounds suffers from some limitations and problems, though. One limitation concerns the amount and cost of the radioactive starting material. This factor necessitates devising synthetic routes to the desired compounds in which the radiolabel can be introduced near the end of the sequence of reactions, so as to secure as high an overall yield of labeled material as possible. At present, numerous labeled compounds are available commercially as starting materials for syntheses. Still, in planning a new synthetic route, it is necessary to consider its compatibility with the specific stalling material available. 

Some points of view with respect to the synthesis of labelled compounds should be emphasized ... 

Synthesis of labelled compounds requires reliable procedures and experience in radiochemistry. However, special kits are available for preparation of labelled compounds without experience in radiochemistry, and automated procedures have been developed for fast syntheses. 

Hot atom reactions can be used for synthesis of labeled compounds. So far this technique has been used primarily for and labeling. For example, an organic gaseous conqx)und is mixed with He and the sample is irradiated with neutrons. The reaction He(n,p) H produces tritium as hot atoms (indicated by the small arrow) with kinetic ergies of approximately 0.2 MeV. These hot atoms react with the organic molecules to produce labeled compounds. An example is the formation of labeled butanol... 

The behavior of iodine at trace levels is often anomalous compared with that at macro concentrations. Because of these anomalies, in radiochemical investigations of iodine, either trace analysis or synthesis of labeled compounds, care must be taken to develop proper procedures to deal with potential problems. At the beginning of this review, it is necessary to briefly discuss the major chemical reactions of iodine, which are of importance to radiochemical studies and may be involved in chemical analysis and isotope production. Also included in this discussion are... 

In addition to the publications cited here, there are numerous papers giving the principles of the synthesis of labelled compounds, appearing along with results in scientific journals of many fields. Only a relatively limited number of descriptions of synthesis of labelled compounds are to be found in the specialized publication. Journal of Labelled Compounds and Radiopharmaceuticals, published by John Wiley Sons. 

The use of isotopically labeled proton donors affords a useful synthesis of labeled compounds. For example, abstraction of a proton from the methyl group of exo-3-acetyl-e do-tricyclo[3.2.1.0 ]octane (5) gave an enolate ion that could abstract a deuterium ion from solvent to produce the monodeuterated compound. Repeated exchange of the methyl protons led to a nearly quantitative yield of trideutero product 6 (Scheme 3.21). 

B. G. Dzantiev, Use of recoil energy of atoms for the synthesis of labelled compounds, in Metody Polucheniya Radioaktivn. Preparatov, Sb. Statei (USSR), 1962, pp. 75-88 Chem. Abstr., 59, 1446 (1963). 

Synthesis of labeled compounds involve all of the classical biochemical and synthetic chemical reactions used in the preparation of nonradioactive chemicals. 

Several generator pairs could potentially be utilized as in vivo systems, presuming the parent nuclide offers the adequate chemical properties for synthesis of labeled compounds and a half-life adequate to the biochemical/physiological process the labeled compound is involved. In this context, stable labeling with Ni and Pd, for instance, is not yet established, whereas there are reliable bifunctional chelators available to bind trivalent parent nuclides such as Ce, °Nd, Ho, and The most intensively studied pair as in vivo generator is Ho/ Dy (Ma et al. 1993 Mirzadeh et al. 1994 Smith et al. 1995). After intravenous injection of [ Dy] DTPA and accumulation of the parent nuclide in bone, no translocation of the daughter Ho was observed subsequent to the P decay of Dy. 

The stable isotopes of carbon, nitrogen, oxygen, and sulphur are available commercially in a variety of chemical forms. In this section, an outline is given of the various methods that are currently used for the separation of stable isotopes. It will be clear that the primary source of isotope, and therefore, in most cases the cheapest available form, is determined by the separation procedure adopted. A discussion of some aspects of the synthesis of labelled compounds follows. Although in a review of this size, this cannot be comprehensive, the methods used and the problems that are raised will be outlined. Some recent developments that increase the choice of chemical form available will be mentioned. 

To the medicinal chemist using stable isotopes, the first problem is the source and choice of a particular compound for the required studies. From the previous part of this section, it will be clear that the form of the separated isotope does not always conform to expectations as the ideal synthetic starting point. It is proposed to give some guidelines on the synthesis of labelled compounds from the raw isotope and to enunciate principles designed to aid the chemist in the most efficient use of his resources. 

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