Applications of titanium-mediated reductive coupling and cyclocarbonylation reactions toward natural product synthesis.

摘要

Previous work in our laboratory has demonstrated not only a synthetic value of tandem reductive cyclization---carbonylation reactions in the preparation of complex molecules but also the interesting stereoselectivity observed therein.; The first part of this work employs the titanium-mediated cyclocarbonylation of tethered dienals for the synthesis of prostaglandin analogues, in particular PGF2alpha and methyl jasmonate. Based on this hetero Pauson-Khand strategy, we have established an efficient racemic route to both the prostaglandin and the methyl jasmonate core skeletons. Moderate to excellent selectivities with regard to the hetero Pauson-Khand reaction were observed in both cases.; The second part of our study leads towards the novel synthesis of the biologically active alpha-methylene-gamma-butyrolactone moiety via titanium mediated hetero Pauson-Khand reaction of allenic aldehyde/ketone substrates. This substructure is embodied in many natural products such as Sarkomycin and Frullanolide which have excellent antibacterial and anticancer activities.; The final part of this study describes the development of the titanium-mediated reductive cyclocarbonylation and an imino-alkyne cross-metathesis strategy towards the synthesis of pyrrolizidine and indolizidine alkaloids respectively. The same substrates were employed in both reaction pathways.