Benzenes, isotopically labelled, synthesis

Synthesis of podophyllotoxin (3.86) in cell culture of Linum album results in yields comparable to those of the most efficient tissue cultures of Podophyllum hexandrum. In order to further improve L. album cultures, Seidel et al. (2002) investigated the biosynthesis of podophyllotoxin (3.86). They fed a number of labeled compounds that to L. album cell cultures to identify which of these compounds could be used as precursors to podophyllotoxin. They determined that the substitution pattern on the benzene ring is critical. The substitution has to be either 3-methoxy, 4-hydroxy, as in ferulic acid (3.33), or, alternatively, 3,4-methylenedioxycinnamic acid (3.90) can serve as precursor. The precursor of podophyllotoxin in L. album appears to be deoxypodophyllotoxin (3.83), based on the higher level of isotope incorporation in the latter compound. This means that 7-hydroxymatairesinol, the precursors of 5-methoxypodophyllotoxin in L. flavum (Xia et al., 2000), is not a precursor of podophyllotoxin in L. album. 

Although isotope exchange by virtue of its simplicity and ability to form compounds of high specific activity is the method of choice for the labelling of tautomeric thiols, a synthetic method is often better suited to other thiols. For example, heating a-toluenethiol with sulphur- S in benzene at 135-140°C for 6-12 h, yields ct-toluenethiol- S with a specific activity of only 2-9%. However, the synthesis of the compound from benzyl-magnesium chloride and sulphur- S yields a-toluenethiol- S... 

Baba, S., and Kawai, K. (1974) Studies on drug metabolism by use of isotopes. XI. Studies on synthesis and physicochemical features of H-labeled /-ephedrine on benzene ring. Yakugaku zasshi. Journal of the Pharmaceutical Society of Japan, 94,783-787. 

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