Synthesis of the dipyrrolopyrazinone core of dibromophakellstatin and related marine alkaloids

The dipyrrolopyrazinone (ABC) core of the phakelline-type pyrrole-imidazole alkaloids from marine sponges was synthesized starting from L-prolinol and 2-trichloroacetylated pyrroles. On oxidation of the condensation product with IBX, immediate cyclization occurs. It was found that the presence of a bromine substituent in the 8-position of the resulting tricyclic N,O-hemiacetal exclusively favors the cis relative configuration at the stereogenic centers C10 and C10a. Via an intermediate tertiary N-acyliminium ion, the pyrazinone core was dihydroxylated by treatment with m-CPBA in the presence of water. The simultaneous functionalization of the C10 and C10a positions is an important step towards the synthesis of the cytotoxic natural product dibromophakellstatin (C) 2002 Elsevier Science Ltd. All rights reserved.