Synthesis of the dipyrrolopyrazinone core of dibromophakellstatin and related marine alkaloids

✍ Scribed by Delphine E.N. Jacquot; Holger Hoffmann; Kurt Polborn; Thomas Lindel

• Book ID: 104251018
• Publisher: Elsevier Science
• Year: 2002
• Tongue: French
• Weight: 92 KB
• Volume: 43
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(02)00600-7

✦ Synopsis

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