RESUMO
The total synthesis of (-)-antrocin and its enantiomer are presented. Antrocin (-)-1 is an important natural product which acts as an antiproliferative agent in a metastatic breast cancer cell line (IC50: 0.6 µM). The key features of this synthesis are: (a) selective anti-addition of trimethylsilyl cyanide (TMSCN) to α,ß-unsaturated ketone; (b) resolution of (±)-7 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 (+)-12 with monomeric formaldehyde and pyridinium chlorochromate (PCC) oxidation for synthesis of essential lactone core in (-)-14; and (d) non-basic Lombardo olefination of the carbonyl at the final step to yield (-)-antrocin. In addition, (+)-9 cyclic ketal diastereomer was converted to (+)-antrocin with similar reaction sequences.
Assuntos
Produtos Biológicos/síntese química , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Lactonas/síntese química , Sesquiterpenos/síntese química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Cianetos/síntese química , Cianetos/química , Feminino , Humanos , Lactonas/química , Lactonas/farmacologia , Metástase Neoplásica , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Estereoisomerismo , Tartaratos/síntese química , Tartaratos/química , Compostos de Trimetilsilil/síntese química , Compostos de Trimetilsilil/químicaRESUMO
Stereoselective total synthesis of anti-fungal cyclopentenone (-)-hygrophorone A12 and cyclopentanone 4-epi-2,3-dihydrohygrophorone H12 were achieved in high overall yields from d-ribose. An aqueous KOH mediated diastereoselective formation of ß-hydroxy ketone with three contiguous chiral centres served as a key step in this synthesis.