Total Synthesis of Mallotusinin.

We describe the total synthesis of mallotusinin that 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. The key features of the total synthesis are: (1) improvements of our previously reported method to synthesize corilagin; (2) an establishment of forming the THDBF skeleton via an unusual intramolecular S N Ar reaction of an HHDP analog, and (3) the application of two-step bislactonization strategy for an HHDP bridge construction into the 2,4- O -THDBF bridge construction. 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 improvement synthesis of corilagin, which enabled the adequate supplement of a corilagin precursor for developing the mallotusinin synthesis. These established methods are expected to development of the synthesis of other ellagitannins with a bridge between the two oxygens of corilagin.