Total synthesis of the multidrug-resistance reversing agent hapalosin

Hapalosin, a new reversing MDR agent, has been synthesized by macrolactamis ation of a linear precursor 2 derived from the coupling of a beta-hydroxy g amma-aminoacid 3 and two hydroxy-esters 4 and 5. The aminoacid 3 was stereo selectively obtained by opening of an anti beta-aminoepoxide while the 3-hy droxyacid 4 was prepared by condensation of a lithium compound with (R)-2-p henyl-propanal followed by oxidation of the phenyl group.