Labelled compounds production

Many applications ia tracer technology require products of high specific activity, ie, compounds having a high degree of substitution of specific atoms with radioisotopes. For many labeled compounds nearly 100% labeling can be achieved at one or more locations ia a molecule usiag... 

Even higher organisms can be used for the production of labeled compounds. Plants, tobacco, or Canna indica for example, when grown in an exclusive atmosphere of radioactive carbon dioxide, [ 002], utilize the labeled precursor as the sole source of carbon for photosynthesis. After a suitable period of growth, almost every carbon atom in the plant is radioactive. Thus, plants can serve as an available source of C-labeled carbohydrates (9). 

The small synthetic scale used for production of many labeled compounds creates special challenges for product purification. Eirst, because of the need for use of micro or semimicro synthetic procedures, the yield of many labeled products such as high specific activity tritiated compounds is often low. In addition, under such conditions, side reactions can generate the buildup of impurities, many of which have chemical and physical properties similar to the product of interest. Also, losses are often encountered in simply handling the small amounts of materials in a synthetic mixture. As a consequence of these considerations, along with the variety of tracer chemicals of interest, numerous separation techniques are used in purifying labeled compounds. 

Consequentiy, phthalocyanines are used extensively ia printing inks and paints. The preponderance of blue and green labeling on products is testament to the popularity of phthalocyanine-based printing inks, and most blue and green cars are the product of phthalocyanine-based paints (see Phthalocyanine compounds). 

An example is the preparation of 18-trideuterio 5a-steroids bearing a side chain at C-17. Labeling of this position with three deuteriums was accomplished by utilizing the Johnson procedure for steroid total synthesis. This synthesis involves, in part, introduction of the 18-angular methyl group by methylation of the D-homo-17a-keto-17-furfurylidene intermediate (243). By substituting d3-methyl iodide in this step, the C/D cis- and ra/J5-18,18,18-d3 labeled ketones [(244) and (245)] are obtained. Conversion of the C/D tra 5-methylation product (245) into 18,18,18-d3-d /-3)8-hydroxy-5a-androstan-17-one (246) provides an intermediate which can be converted into a wide variety of C-18 labeled compounds of high (98%) isotopic... 

Table V indicates the incorporation and distribution of labeled compounds into kasugamycin (1), when they are added during the production of this antibiotic. Glucose is incorporated into kasugamine and d-inositol. Mt/o-inositol is mainly incorporated into the d-inositol moiety, suggesting the synthesis of d-inositol moiety through myo-inositol or its derivative from glucose or other carbon sources.

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... 

The use of deuterated organosilicon hydrides in conjunction with proton acids permits the synthesis of site-specific deuterium-labeled compounds.59 126 221 Under such conditions, the deuterium atom in the final product is located at the charge center of the ultimate carbocation intermediate (Eq. 62). With the proper choice of a deuterated acid and organosilicon hydride, it may be possible to use ionic hydrogenation in a versatile manner to give products with a single deuterium at either carbon of the original double bond, or with deuterium atoms at both carbon centers.127... 

In Fischer-Tropsch synthesis the readsorption and incorporation of 1-alkenes, alcohols, and aldehydes and their subsequent chain growth play an important role on product distribution. Therefore, it is very useful to study these reactions in the presence of co-fed 13C- or 14 C-labeled compounds in an effort to obtain data helpful to elucidate the reaction mechanism. It has been shown that co-feeding of CF12N2, which dissociates toward CF12 and N2 on the catalyst surface, has led to the sound interpretation that the bimodal carbon number distribution is caused by superposition of two incompatible mechanisms. The distribution characterized by the lower growth probability is assigned to the CH2 insertion mechanism. 

Specific activity of a radiopharmaceutical may be defined as the amount of radioactivity per unit mass of a radioisotope or a labeled compound. For example, if 100 mg l3lI-labeled albumin contains 150 mCi l3lI radioactivity, its specific activity would be 150/100, i.e., 1.5 mCi/mg. Specific activity is usually expressed in units such as Ci/g, mCi/mg, or MBq/mg. It is also expressed in terms of the radioactivity per mole of a labeled compound, e.g., mCi/mole, MBq/mole, mCi/pmole, or MBq/p,mole. Specific activity is usually provided on the product label. 

This procedure illustrates a general method for converting substituted pyrylium salts to nitrobenzene derivatives. The reaction has been the subject of several reviews. - The yields are generally high, and under these conditions only a single product is formed, in contrast to the nitration of 1,3,5-triphenyl-benzene. The preparation of 2,4,6-triphenylnitrobenzene from the corresponding pyrylium salt eliminates isomer separation problems, which are encountered when the direct nitration procedure is used. Also, labeled compounds can readily be prepared by this method. ... 

Another type of abbreviation—a bolded number, sometimes followed by a letter—is used to label reagents, products, or other compounds that are mentioned more than once in the text. (This is a useful convention because compounds can often be more than 100 characters in length ) Bolded numbers are also used to label species in reactions and schemes, so that the species can later be referred to by number. In the text, the bolded number is introduced, sometimes in parentheses, immediately after the first usage of the full name, like other types of abbreviations. Subsequent references to the compound are by bolded number (and possibly a letter) only, without the full name and without parentheses. Numbers are assigned sequentially if more than one compound is labeled in the text. 

Reetz and coworkers developed a highly efficient method for screening of enantioselectivity of asymmetrically catalyzed reactions of chiral or prochiral substrates using ESI-MS [60]. This method is based on the use of isotopically labeled substrates in the form of pseudo-enantiomers or pseudo-prochiral compounds. Pseudo-enantiomers are chiral compounds which are characterized by different absolute configurations and one of them is isotopically labeled. With these labeled compounds two different stereochemical processes are possible. The first is a kinetic separation of a racemic mixture, the second the asymmetric conversion of prochiral substrates with enantiotopic groups. The conversion can be monitored by measuring the relative amounts of substrates or products by electrospray mass spectrometry. Since only small amounts of sample are required for this method, reactions are easily carried out in microtiter plates. The combination of MS and the use of pseudo-enantiomers can be used for the investigation of different kinds of asymmetric conversion as shown in Fig. 3 [60]. 

The IR spectrum of 133 was obtained by laser vaporization of graphite and subsequent condensation of the reaction products in solid argon at 10 K. However, only the most intense mode at 1695 cm could be detected. " The antisymmetric stretching vibration of the linear isomer 132 is observed at 1952 cm . " " The assignment could be corroborated by measuring the spectra of isotopically labeled compounds. In a more recent theoretical work, the UV spectra of 133 and 134 were calculated, " " but experimental data are lacking so far. 

Formic acid, methyl formate, and CO were detected when photoreduction was performed in Ti silicalite molecular sieve using methanol as electron donor.173 Mechanistic studies with labeled compounds indicated, however, that CO originates from secondary photolysis of formic acid, whereas methyl formate emerges mainly from the Tishchenko reaction of formaldehyde, the initial oxidation product of methanol. 

As an example the carrier addition method 2 is described in more detail in the appendix since this is important for establishing the radiochemical purity of labelled compounds. The other two procedures are similar in principle and are described elsewhere (29). The technique has been used to measure the products of initiator side reactions in azoiso-butyronitrile initiated polymerizations (30—33) and in benzoyl peroxide decomposition (34) and is capable of much wider application than it has so far received. 

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