Ortho tritiation

The investigators then tested ortho-tritiated phenylalanine, which would be expected to label the intermediate (68) with tritium as indicated. If intermediates of the crinine type are involved, a 50% loss of tritium with respect to an internal standard would be expected as a result of the phenol coupling process. Surprisingly, mesembrine was produced without loss of tritium and the alkaloid was found to have the tritium labelling pattern shown in (76) (Scheme 12). 

Figure 3.46 Representative acylanilide substrates subject to ortho-tritiation...

Figure 3.47 Representative nitro substrate subject to ortho-tritiation and schematic drawings of other nitrogen-bases exchange-mediating functions...

In the first the mode of incorporation of the amino phenol O-methyl-norbelladine 343 into 10 was examined. Thus, tritium labels were inserted ortho and para to the phenolic hydroxy groups of 343 by base-catalyzed exchange with tritiated water under conditions ensuring equal labeling in all exchangeable positions. Norpluviine biosynthetized from multiply labeled 343 in Texas daffodil was selectively degraded to locate the tritium labels. 

The reactivities differ for ortho, meta, and para positions of toluene. In anthranilic acid (10), positions 3 and 5 in the molecule possess 49.8 and 27.4% of the total activity thus, tritium incorporation tends to be highest at positions of highest electron density.35 In isopropanol,35 the hydroxyl group incorporates approximately three times as much isotope as any other hydrogen position, while tritiation of the secondary C-H is slightly more efficient than the primary C-H. In the aliphatic esters of aromatic carboxylic acids, the aryl hydrogens tritiate ten times faster than alkyl hydrogens.10,36... 

The conversion of the o-methoxyphenol to the methylenedioxy group may occur late in the biosynthetic pathway. Tritiated norpluviine is converted to tritiated lycorine by the Deanna Durbin daffodil. This transformation not only demonstrates the conversion of an o-methoxyphenol to the methylenedioxy group but also indicates that the C-2 hydroxyl group of lycorine is derived by allylic oxidation of either norpluviine or caranine. This late-stage hydroxylation was suspected when it was found that hydroxynorbelladine (CCXXVIII R,Ri,R2,Rs = H OH instead of H ortho to RgO) was incorporated into lycorine with extremely low efficiency. 

Barton et al. (204) have prepared two labeled 0-methyI laudanosolines. One is the already known 4 -0-methyllaudanosoline (CXLII Ri=H, R2 = CH3) (mp 120°-122°) (205) with in the iV-methyl group the other, the 6-0-methyllaudanosoline (CXLII Ri = CH3, R2 = H), which was synthesized by the Bischler-Napieralski route. Its tribenzyl derivative (mp 62°) was debenzylated to the triphenolic base which deteriorates in air. Tritium was introduced ortho and para to the phenolic hydroxyl groups by exchange with tritiated water. 

Already mentioned have been labeling of aromatic (and some heteroaromatic) rings ortho to carbonyl-based functions such as ketones, esters, amides and anilides, and heteroaromatic functions such as 2-pyridyl and the fused analog benzoquinoline. Modest extensions of the range of carbonyl-based functions to tritiation of ureas have been reported , including 124... 

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