Chemistry of renieramycins. Part 12: An improved total synthesis of (±)-renieramycin G

An improved total synthesis of (±)-renieramycin G (1g) from readily available 2-hydroxy-3-methyl-4,5-dimethoxybenzaldehyde (7) in 21 steps (6.3% overall yield) is described. The synthesis features the concise construction of a pentacyclic framework using the stereoselective Pictet–Spengler type cyclization reaction of lactam (25) with ethyl diethoxyacetate, followed by the base-catalyzed epimerization of the C-1 stereo center of aldehyde (30a). The results of cytotoxicity studies are also presented.