Synthesis of [13C]‐ and [2H]betulin for biological transformations
Selective acetylation of 1 at C-28 afforded the monoacetate 2, which was oxidized to the 3-oxo compound 8. H,D exchange at C-2 in 8 followed by reduction with LiAlH4 led to [2-2H]-betulin (5). Reduction of 8 with NaBD4 or LiAlD4 yielded [3-2H]betulin (6) besides different amounts of the respective 3α-hydroxy compound 7. For the introduction of a CD2 or 13CH2 unit at C-29 betulin diacetate 4 was ozonolyzed to give the known compound 10, which was treated either with CD2Br2, Zn, and TiCl4 in THF to yield the [29-2H2] compound 11 or with [13C]methyltriphenylphosphonium iodide and potassium tert-butoxide to afford the [29-13C]-labeled compound 11. Solvolysis of 11 and 13 with methanol and potassium carbonate afforded the desired compounds [29-2H2]betulin (12) and [29-13C]betulin (14).