Developing Neolignans as Proangiogenic Agents: Stereoselective Total Syntheses and Preliminary Biological Evaluations of the Four Guaiacylglycerol 8-O-4′-Coniferyl Ethers

摘要

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 auxiliary-controlled 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.