First Total Synthesis of Neostrictinin

Abstract

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 [a]

The beauty of biocatalysis: sustainable synthesis of ingredients in cosmetics

“…115,119–122 More recently total syntheses of some ellagitannins have been achieved chemically. 123–127…”

Total Synthesis of Mallotusinin

“…[13] On the other hand, the twostep bislactonization strategy entailsm ono-acylation of diol 5 with HHDP-derived acid anhydride 6,f ollowed by intramolecular lactonization of produced seco-acid 7 (Scheme 1b). This methode nabled the formation of 1,2-O-(S)-, [9d] 1,2-O-(R)-, [9a, c] 4,6-O-(S)-, [9c] and 4,6-O-(R)-HHDP bridges, [14] the construction of which by using double esterification strategy was difficult. We expectedt hat either of the two strategies would allow the formation of the 2,4-O-THDBF bridge of 1.T herefore, the requisite fragments for the synthesis of 1 are 2,4-diol 8,w here the phenolic hydroxy groups of corilagin( 2)a re protected, and dicarboxylic acid 9 with aT HDBF moiety( Scheme1c).…”

“…On the other hand, the two‐step bislactonization strategy entails mono‐acylation of diol 5 with HHDP‐derived acid anhydride 6 , followed by intramolecular lactonization of produced seco ‐acid 7 (Scheme 1 b). This method enabled the formation of 1,2‐ O ‐( S )‐, [9d] 1,2‐ O ‐( R )‐, [9a, c] 4,6‐ O ‐( S )‐, [9c] and 4,6‐ O ‐( R )‐HHDP bridges, [14] the construction of which by using double esterification strategy was difficult. We expected that either of the two strategies would allow the formation of the 2,4‐ O ‐THDBF bridge of 1 .…”

Verification of Biaryl-Structure Axial Chirality Produced in Ellagitannins by Chemical Oxidation

“…Transformation of the obtained 13a / b to natural products determined their axial chiralities of the HHDP group (details in the Supporting Information). Conversion of 13a / b to the corresponding synthetic intermediates , achieved the formal synthesis of strictinin from ( S )- 13a / b and that of neostrictinin ( 10 ) from ( R )- 13a / b , respectively.…”