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.
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Laboratoire de Pharmacognosie de l'Université René Descartes-UMR 8638, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, 75006 Paris, France.
Michel
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Tillequin
F
F
Koch
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M
Pierré
A
A
Atassi
G
G
D000175:Acronine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210 / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C102518:1,2-diacetoxy-1,2-dihydroacronycine; C111686:1,2-dihydroxy-1,2-dihydroacronycine; D000972:Antineoplastic Agents, Phytogenic; D000175:Acronine