Tritiated formaldehyde

The flavoenzyme UDP-galactop)ranose mutase (UGM) plays a key role in the cell wall biosynthesis of many pathogens, including Mycobacterium tuberculosis. McNeil and co-workers developed a microtiter plate assay for UGM (O Scheme 14) [157]. The assay is based on the release of tritiated formaldehyde from UDP-galactofuranose but not UDP-galactopyranose by periodate and was used to identify a uridine-based enzyme inhibitor from a chemical library. The potent inhibitor 320KAW73 (IC50 = 6 pM) was identified. 

Tritiated formaldehyde is also useful in Mannich reactions. Examples of such applications include the preparation of the topoisomerase-1 inhibitor 364 by condensation of tritiated formaldehyde and dimethylamine with 10-hydroxycamptothecin 1363). the reaction with acetone and diethylamine to give 4-diethylamino-4-[ H2]butan-2-one 365 which was further converted upon heating with thebaine (366) to the morphine derivative 367 (specific activity of 46 Ci/mol). Furthermore, condensation of aqueous deuterated formaldehyde with allyltrimethylsilane to prepare the 2,6-doubly labeled piperidine 368. as indicated , would be expected to work equally well with tritiated formaldehyde. 

Recently, the enzymatic formation of folinic acid has been utilized to synthesize radioactively labeled products.34 The preparation of 5-formyl tetrahydrofolate, 9,3, 5 -3H and 5-formyl-14C-tetrahydrofolate starts with tritiated folic acid, which is reduced to dihydrofolate, incubated in the presence of formaldehyde, dihydrofolate reductase, and NADPH, and finally incubated with 5,10-methylenetetrahydrofolate dihydrogenase. The product,... 

Preparation of formaldehyde by photochemical condensation of carbon monoxide and tritiated hydrogen, and the synthesis of a tritiated morphine derivative Lane, A. C. McCoubrey, Arthur Peaker, R. 

---