Synthesis of Natural (−)-Antrocin and Its Enantiomer via Stereoselective Aldol Reaction

摘要

The total synthesis of (−)-antrocin and its enantiomer are presented. Antrocin (−)- is an important natural product which acts as an antiproliferative agent in a metastatic breast cancer cell line (IC : 0.6 M). The key features of this synthesis are: (a) selective anti-addition of trimethylsilyl cyanide (TMSCN) to -unsaturated ketone; (b) resolution of (±) using chiral auxiliary L-dimethyl tartrate through formation of cyclic ketal diastereomers followed by simple column chromatography separation and acid hydrolysis; (c) substrate-controlled stereoselective aldol condensation of (+)- with monomeric formaldehyde and pyridinium chlorochromate (PCC) oxidation for synthesis of essential lactone core in (−)- ; and (d) non-basic Lombardo olefination of the carbonyl at the final step to yield (−)-antrocin. In addition, (+) cyclic ketal diastereomer was converted to (+)-antrocin with similar reaction sequences.