Synthesis of [¹³C]‐ and [²H]betulin for biological transformations

Abstract

Abstract 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 LiAlH 4 led to [2‐ 2 H]‐betulin ( 5 ). Reduction of 8 with NaBD 4 or LiAlD 4 yielded [3‐ 2 H]betulin ( 6 ) besides different amounts of the respective 3α‐hydroxy compound 7 . For the introduction of a CD 2 or 13 CH 2 unit at C‐29 betulin diacetate 4 was ozonolyzed to give the known compound 10 , which was treated either with CD 2 Br 2 , Zn, and TiCl 4 in THF to yield the [29‐ 2 H 2 ] compound 11 or with [ 13 C]methyltriphenylphosphonium iodide and potassium tert ‐butoxide to afford the [29‐ 13 C]‐labeled compound 11 . Solvolysis of 11 and 13 with methanol and potassium carbonate afforded the desired compounds [29‐ 2 H 2 ]betulin ( 12 ) and [29‐ 13 C]betulin ( 14 ).