Developing neolignans as proangiogenic agents: Stereoselective total syntheses and preliminary biological evaluations of the four guaiacylglycerol 8-O-4'-coniferyl ethers

Abstract

Stereoselective total syntheses of the four stereoisomeric forms of guaiacylglycerol 8-O-4′-coniferyl ether, viz., compounds 1, ent- 1, 2, and ent- 2, have been established. The key step involves an Evans/Seebach auxiliarycontrolled and syn-selective aldol process followed, in the reaction sequences leading to the anti-compounds, by a Mitsunobu reaction involving a benzylic alcohol residue. The proangiogenic properties of the synthetic materials were evaluated in a human microvascular endothelial cell tubule formation assay, thus revealing that they are all active, with the 8S-configured compounds 1 and 2 being the most potent.