| Summary: | The total synthesis of (−)-antrocin and its enantiomer are presented. Antrocin (−)-<b>1</b> is an important natural product which acts as an antiproliferative agent in a metastatic breast cancer cell line (IC<sub>50</sub>: 0.6 <i>μ</i>M). The key features of this synthesis are: (a) selective anti-addition of trimethylsilyl cyanide (TMSCN) to <i>α,β</i>-unsaturated ketone; (b) resolution of (±)<b>-7</b> 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 (+)-<b>12</b> with monomeric formaldehyde and pyridinium chlorochromate (PCC) oxidation for synthesis of essential lactone core in (−)-<b>14</b>; and (d) non-basic Lombardo olefination of the carbonyl at the final step to yield (−)-antrocin. In addition, (+)<b>-9</b> cyclic ketal diastereomer was converted to (+)-antrocin with similar reaction sequences.
|
|---|