Non‐Enzymatic Oxidation of a Pentagalloylglucose Analogue into Members of the Ellagitannin Family

Abstract

The occurrence of more than 1000 structurally diverse ellagitannins has been hypothesized to begin with the oxidation of penta-O-galloyl-β-d-glucose (β-PGG) for the coupling of the galloyl groups. However, the non-enzymatic behavior of β-PGG in the oxidation is unknown. Disclosed herein is which galloyl groups tended to couple and which axial chirality was predominant in the derived hexahydroxydiphenoyl groups when an analogue of β-PGG was subjected to oxidation. The galloyl groups coupled in the following order: at the 4,6-, 1,6-, 1,2-, 2,3-, and 3,6-positions with respective S-, S-, R-, S-, and R-axial chirality. Among them, the most preferred 4,6-coupling reflected the what was observed for natural ellagitannins. A new finding was that the second best coupling occured at the 1,6-positions. With the detection of a 3,6-coupled product, this work demonstrated that even ellagitannin skeletons with an axial-rich glucose core may be generated non-enzymatically.

Total Synthesis of Mallotusinin

“…The most important task for the efficient synthesis of 2 was to establish a method for constructing a 3,6‐ O ‐( R )‐HHDP bridge on the glucose moiety. Recently, we succeeded in constructing a 3,6‐ O ‐( R )‐HHDP bridge through oxidative phenol coupling of penta(4‐benzylgalloyl)‐β‐glucose; however, the adoption is unreasonable due to low yields [9a] . Flipping the pyranose ring from the inherent equatorial‐rich conformation to an axial‐rich conformation is unfavorable due to 1,3‐diaxial repulsion, hindering the formation of the 3,6‐ O ‐( R )‐HHDP bridge on d ‐glucose.…”

“…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 .…”

1,2,3,4,6‐Penta‐O‐galloyl‐β‐D‐glucopyranose: Its Anti‐Inflammatory and Antibacterial Properties

“…The compound can occur as one of two possible stereoisomers: 1,2,3,4,6‐penta‐O‐galloyl‐α‐D‐glucopyranose (α‐PGG) and 1,2,3,4,6‐penta‐O‐galloyl‐β‐D‐glucopyranose (β‐PGG) which are differ linkages between the galloyl group and the anomeric center of the glucose core at C1’ atom (Scheme ) . Considering the properties, such as antioxidative, antimutagenic, antineoplastic and antibacterial, PGG have plenty of potential applications in medicine ,…”

Total Synthesis of Phyllanemblinin B

“…In 2017, we conducted a nonenzymatic study that involved the investigation of the chemical oxidation of 7 possessing partially protected galloyl groups. 8 The study established that the galloyl groups tended to couple in the following order:…”