Tritium loss

In the more than 5 years since the detonation there has been a net loss of tritium from the Sedan postshot environment. The integrated values for the 20A transect provide some indication of the rate of loss, but a detailed analysis of tritium losses will be made in a future report. Table I shows the depth-integrated tritium value in curies per square... 

Benzodiazepine Bases.—It is known that phenylalanine is an intact precursor for the benzodiazepine bases cyclopenin (124) and cyclopenol (125), via (122) and (123), in Penicillium cyclopium cultures.102 Examination of the stereochemical course of the necessary tritium loss from C-3 of the precursor amino-acid on formation of (124) has given a surprising result more than half of the tritium was... 

All soil types showed a similar pattern of tritium loss to leachate with time. After a short period of about a month, the tritium concentration in the leachate peaked at about 100 - 200 mBq ml It then fell over the next month or so to a low and fairly constant value of about 10-20 mBq m Where measurements were made, there was no significant difference between the aqueous and total tritium concentration. It would therefore be reasonable to assume that all of the tritium lost via downward leaching was in the form of tritiated water. Although tritium could be measured in the leachate, the overall flux did not account for all of the losses as broadly implied from the measurements in soils from the containers. Table 4 shows that for all soil types, only about one third of the decrease in soil activity can be accounted for in the leachate. 

C-3. The results show that the 3-pro-S hydrogen is lost on formation of cryp-toechinulin A (100). From the stereochemistry of the double bond in (100) it follows that hydrogen loss occurs with formal cis stereochemistry. [The incorporation of the [3- H]tryptophan samples into echinulin (96) occurred without tritium loss which, although expected, contrasts with the observation of partial loss of 3-/ -tritium in the transformation of phenylalanine into gliotoxin and of tyrosine into mycelianamide. ]... 

Unexpectedly, however, each of the precursors examined showed a 50% tritium loss on incorporation into mesembrenol (119), the residual tritium being equally distributed between H-5 and H-7a. On the basis of the generalized bis-spirodienone intermediate (120) the results are consistent with an internal conjugate addition of nitrogen followed by stereospecific j8-protonation of the resulting enolate at C-7 (Scheme 8). Since tritium is equally distributed between H-5 and H-7a in (119)... 

The validity of the above scheme was further explored with cadaverine samples chirally labelled with tritium at C-1. (The samples were obtained by decarboxylation of L-lysine mediated by L-lysinedecarboxylase from Bacillus cadaveris. The absolute configuration of the two materials is unknown and they were accordingly named [L4- H]- and [15- H]-cadaverine.) The labelling pattern of the derived N-methylpelletierine (22) was in accord with stereospecific oxidative deamination to A -piperideine (30) and in agreement with the proposed model. Both cadaverine samples afforded iV-methylpelletierine (22) with a label at C-6 but only [l/4- H]cadaverine labelled C-2. (The puzzling loss of 25% of the tritium from non-chirally labelled [l- C,l- H]cadaverine on incorporation into N-methylpelletierine is now explained in terms of this model, the tritium loss being exactly as predicted. It seems that subsequent elaboration of N-methylpelletierine (22) to pseudopelletierine (24) is accompanied by preferential tritium retention at C-6 by a primary isotope effect. )... 

Label from methionine was roughly equally split between the two halves of anthramycin[normal and heavy bonding in (166)]. A mixed labelled sample was shown to give the aromatic C-methyl of anthramycin without tritium loss whilst incorporation into the acrylamide-proline moiety was with omplete loss of tritium. The inference from this was that methionine gives the carbonyl carbon of this moiety. 

More significantly [l- C,2- H]methionine [as (213)] was incorporated with almost complete tritium loss and so methionine (213) and S-adenosylmethionine cannot be the ultimate precursors for (212). Further, 2,4-diaminobutyric acid... 

To overcome the extensive tritium loss encountered with D-[6- Hl-4FG, we have now synthesized 4-deoxy-4-fluoro-D-[U- C]-glucose (D-[U- C]-4FG) by the action of diethylaminosulphur trifluoride on methyl 2,3,6-tri-Q-benzoyl- 04 -D-[U- C]galactopyranoside (Sbrissa and Taylor, unpublished results). Table I summarizes the distribution of radioactivity in various fractions... 

Samples of (26), (23), and (25), doubly labelled as shown ( = C), were examined as precursors for tylophorine (30), tylophorinidine (29), and tylophorinine (28) and were found to be incorporated into each alkaloid at a similar level, indicating a close biosynthetic relationship. The changes in isotope ratio were consistent with the necessary tritium loss from sites in (23) and (25) which became hydroxylated in the course of biosynthesis, and from C-6 in (26) during phenol coupling. It follows that (23), (25), and (26) are intact precursors for (28),... 

Several factors influence the half-time of tritium loss from the film tubes (Table 1). As size of the air space above the scintillator (and therefore the total exchange surface area of the tube) increases, the rate of loss of THO increases. This indicates that THO not only diffuses out of the tube directly from the solvent phase but from the gas phase above the scintillator as well. Solvent systems which increase the water vapor pressure in the enclosed tube by decreasing the soliiiility coefficient of water, micelle stability or micelle surface area to volume ratio would be eiqjected to decrease the half-time for THO loss. This would e q)lain the difference in half-times between the toluene and xylene derivative based scintillation solutions. 

As the percent water in the liquid scintillation solution is increased from 0.5 to 30, the half-time for tritium loss from film tubes containing either Liquiscint or TT-21 increases (figure 3). At water concentrations greater than 30%, little additional increase in half-time was observed. Although not evident in figvire 3, because of the short halftimes, the relationship between half-time of tritium loss and percent water is similar for air ejq>osed scintillator solutions and film tubes (i.e. the half-time increases up to a plateau around 30% water). The increase in half-time (and decrease in tritium efflux rate) from 0 to 30% water presumably is due to the decrease in specific activity in the water micelles and in the water vapor phase. The relative stability in half-time at water concentrations greater than 30% is unexplainable although it may reflect alterations in the gel matrix. 

Tritium ( H) and with half-lives of 12.26 years and 5600 years respectively, are the most commonly used radioactive isotopes. They are used extensively to monitor the uptake of precursors into metabolites and to determine the fates of individual hydrogens or carbons in a precursor during biosynthesis. Tritium finds particular application in this latter regard because any number of proton additions/removals and rearrangements may occur in the course of the biotransformation of precursor into metabolite. (Tritium loss is normally measured by reference to a label in the precursor which is known not to be lost during biosynthesis.)... 

Tritium at C-2 and C-6 of lysine is retained on formation of sedamine 6.21) [10, 11]. These results, supported by those with [ N]-labelled samples of lysine, indicate that alkaloid formation involves retention of the C-6 amino-group and loss of the one at C-2. Loss of the C-6 amino group would require oxidation of C-6 and tritium loss, but removal of the other amino-group is not expected, necessarily, to result in tritium loss from C-2. The reaction may be one of deaminative decarboxylation (see below) leading to... 

The validity of (6.267) as a biosynthetic intermediate is supported by the isolation of simple secodine (6.268) derivatives from plants and by the specific incorporation of labelled secodine (6.268) into vindoline (6.244) the tritium loss from (6.268) labelled in the dihydropyridine ring on transformation into vindoline (6.244) is consistent with involvement of secodine (6.268) via a more highly oxidized intermediate [as (6.267) [187]. 

There are examples of the uncatalyzed exchange with HHO at the a-positions of steroidal ketones . The ketone functions were immediately subjected to synthetic transformations in order to prevent tritium loss by back-exchange. The C2 positions of imidazole-containing pharmaceuticals have been similarly exchanged in this case, the half-time for loss of the tritium label was determined to be 2.4 days at 37 °C and pH 7, adequate for the intended study. This figure is similar to that measured for [imidazole-2- H]histidine, namely 2.8 days at 37 °C and pH 8.2. 

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