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LABELED SYNTHESIS OF 0,0-DIETHYL 0-p-NITR0PHENYLPH0SPHATE-(3-(5)-3H) M. Shimoni, J. Azran, A. Cohen, Y. Hagag and 0. Buchman
Toxic organic phosphorus compounds act as powerful inhibitors of cholinesterase. This enzyme hydrolyses acetylcholine which is essential in the transmission of nerve pulses
Paraoxon or diethyl p-nitrophenylphosphate, the oxygen analog of parathion, was labeled with tritium. The nitro function of the molecule is very sensitive to hydrogen (tritium) and undergoes rapid reduction to the amino derivative. Therefore, the synthesis must start with its first step already "hot". In order to synthesize sufficient product to perform further steps, the tritium was mixed with hydrogen. This limited the possibility of providing the desired compound at high specific activity. Starting from m-bromophenol, the steps were performed as follows:
3H Dioxane, NEt., A"ZT\ NaNO* OH -T—^ (OV°H —-*- ^nOV-oH H2 + H2,cat. H S0 + 'H2,cat. \ / 2 4 ) ' (3H) H )—\ (Et0) P0Cl ) . 2 .OEt o2N_^M,„_J_02N._
The last step led to a very pure product, chemically and radiochemically, and no further purification was needed. The specific activity was 1.3 Ci/mmol.
REFERENCE: 1. Hall, S. A., Advan. Chem. Ser., JL, 150 (1950)
STRUCTURALLY SENSITIVE ANTIDEPRESSANTS LABELED WITH TRITIUM 0. Buchman, M. Shimoni, J. Azran, A. Cohen and Y. Hagag
In the expansion of our program of tritium labeling of anti depressant drugs having a tricyclic structure, we found that it was - 185 -
(2) not possible to apply nonspecific labeling, catalyzed by PdON , to all of them. Molecules with one or two double bonds or an etheral linkage underwent saturation or decomposition before isotopic exchange occurred. Tritiation on these sensitive compounds by various labeling methods was attempted and the experimental results are summarized in Table 1.
Table 1 Comparison of results of different tritiation methods
Compound Tritiation method Results Specific activity (Ci/mmol) (3) Amitriptyline debromination 10,11-labeling 14.3 Nortriptyline debromination 10,11-labeling 15.8 Doxepin deiodination 10-labeling 19.6 Opipramol deb romination 10,11-saturation — Pt02 in situ(4) 10,11-saturation — Cyclobenzaprine debromination 10,11-labeling with formation of amitriptyline 15.0 Pd/C 10,11-labeling with formation of amitriptyline 19.5 Pd/C + base no reaction — Cyprohep tadine debromination 10,11-saturation — PdO in situ(2) 10,11-saturation — PtC-2 in situ nonspecific labeling 2.0 PtC-2 + base (in situ) nonspecific labeling 2.8 Hepzidine PdO in situ nonspecific labeling 3.4 debromination decomposition — deiodination decomposition ——
REFERENCES: 1. Shimoni, M., Cohen, A., Hagag, Y. and Buchman, 0., in: IA-1364 1981, p. 204- 2. Buchman, 0., Pri-Bar, I. and Shimoni, M., J. Label. Compounds Radiopharm., 14, 155 (1978) 3. Buchman, 0., Blitzblau, M., Cohen, A., Hagag, Y., Pri-Bar, I. and Shimoni, M., in IA-1356, 1980, p. 228. 4. Buchman, 0., Pri-Bar, I., Shimoni, M. and Smoskowitz, L., J. Label. Compounds, 10_, 345 (1974)