First Total Synthesis of Neostrictinin

Herein, we describe the first total synthesis of neostrictinin, a natural ellagitannin bearing a (R)‐hexahydroxydiphenoyl (HHDP) bridge between the 4‐ and 6‐oxygens of d‐glucose. Among the multitude of 4,6‐O‐HHDP bridged ellagitannins, (R)‐axial chirality of the HHDP bridge is quite rare as it is less stable than the corresponding (S)‐isomer. The labile bridge was constructed using a two‐step bislactonization that involved: (1) monoacylation of the primary alcohol of ethyl 2,3‐O‐benzyl‐1‐thio‐β‐d‐glucopyranoside using protected (R)‐hexahydroxydiphenic anhydride and (2) intramolecular lactonization of the obtained seco acid by treatment with a Mukaiyama condensation reagent (2‐chloro‐N‐methylpyridinium iodide) and 2,6‐lutidine. Structural confirmation of the synthesized neostrictinin and the preparation of its epimer are also reported. We achieved the first total synthesis of neostrictinin, a rare ellagitannin bearing a 4,6‐O‐(R)‐hexahydroxydiphenoyl bridge, via two‐step bislactonization. The latter intramolecular lactonization proceeded under Mukaiyama reaction conditions to form the uncommon bridge efficiently. Subsequent three‐step reaction including anomeric galloylation completed the synthesis.