Concise Total Synthesis of (±)-Makaluvamine F and Its Derivatives.

A concise gram-scale total synthesis of (±)-makaluvamine F was accomplished. The left segment, 2-aminodihydrobenzothiophene possessing an N,S-acetal moiety, was prepared using commercially available 2-fluoro-4-methoxybenzaldehyde in 6 steps via Curtius rearrangement. Subsequent condensation of the 2-aminodihydrobenzothiophene segment with a pyrroloiminoquinone segment completed the total synthesis of makaluvamine F, which was achieved in a 23% overall yield via a longest linear sequence of 7 steps. The versatility of the synthetic route involving the Curtius rearrangement was demonstrated by applying it to synthesize several unnatural makaluvamine F derivatives.