Synthesis of sulfur-containing polybromoindoles from the marine alga Laurencia brongniartii

The marine alga Laurencia brongniartii produces thiobromoindoles and 3,3 & PRIME;-bisindoles, structural motifs rare outside this genus. A gram scale synthesis of methyl 4,6-dibromoindole-3-carboxylate followed by facile hydrolysis-decarboxylation provided a scalable route to glossobalol (4,6-dibromoindole). Methylthiolation of glossobalol followed by a [1,2]-sulfide shift gave the natural product 2-(methylthio)glossobalol that upon oxidative homocoupling (FeCl3-O2) forged the hindered bihetaryl bond, affording the natural product 2,2 & PRIME;-bis (methylthio)-3,3 & PRIME;-bisglossobalol. The C2-sulfide plays a crucial role in Fe(III)/O2-mediated oxidative coupling, providing insight into the biosynthesis of these fascinating natural products.

Automated summary

This study successfully synthesized a rare structure in marine algae and elucidated the biosynthetic pathway of its natural product through synthesis.