Chiral dihydroxylation of acronycine: absolute configuration of natural cis-1,2-dihydroxy-1,2-dihydroacronycine and cytotoxicity of (1R,2R)- and (1S,2S)-1,2-diacetoxy-1,2-dihydroacronycine

Sharpless asymmetric dihydroxylation of acronycine (1) gave (1R, 2R)-1,2-dihydroxy-1,2-dihydroacronycine (2) and (1S,2S)-1, 2-dihydroxy-1,2-dihydroacronycine (3), which allowed determination of the absolute configuration of natural cis-1,2-dihydroxy-1, 2-dihydroacronycine as 1R,2R. The cis isomer had been previously isolated from various Sarcomelicope species. Benzylic reduction of isomers 2 and 3 gave the alcohols 4 (2R) and 5 (2S), respectively. Acetylation of 2 and 3 afforded the corresponding esters 6 and 7. No significant difference of cytotoxicity was observed between these (1R,2R)- and (1S,2S)-enantiomers and the recently described, highly active racemic cis-1,2-diacetoxy-1,2-dihydroacronycine, when tested against L-1210 cells in vitro.