Total Synthesis of Mallotusinin

The total synthesis of mallotusinin, which bears a tetrahydroxydibenzofuranoyl (THDBF) bridge between the 2‐oxygen and 4‐oxygen of glucose on corilagin with a 3,6‐ O ‐( R )‐hexahydroxydiphenoyl (HHDP) bridge, is described. The key features of the total synthesis are: 1) improvements of our previously reported method to synthesize corilagin; 2) establishment of the THDBF skeleton via an unusual intramolecular S N Ar reaction of an HHDP analogue, and 3) the application of a two‐step bislactonization strategy for a HHDP bridge construction into the 2,4‐ O ‐THDBF bridge. Oxidative phenol coupling of 1,2,4‐orthoacetyl‐3,6‐di‐(4‐ O ‐benzylgalloyl)‐α‐ d ‐glucopyranose and the orthoester cleavage of the coupling product without the pyranose‐furanose ring transformation are key reactions for the improved synthesis of corilagin, which enabled the adequate supply of a corilagin precursor that was required to develop the mallotusinin synthesis. These established methods are expected to help develop the synthesis of other ellagitannins with a bridge between the two oxygens of corilagin.