Studies toward the synthesis of luminacin D: assembly of simplified analogues devoid of the epoxide displaying antiangiogenic activity

[reaction: see text] A series of structurally simplified luminacin analogues devoid of the epoxide ring are assembled in a stereocontrolled manner from 2,4-dimethoxybenzaldehyde using a syn-selective aldol reaction as the key step. The success of the approach is critically dependent on the nature and extent of the alcohol protecting groups. The synthetic analogues inhibit VEGF-stimulated angiogenesis in an in vitro assay indicating that the epoxide is not essential for biological activity in this compound class.