Reinvestigation of the Stereochemistry of the C-Glycosidic Ellagitannins, Vescalagin and Castalagin

Abstract

The stereochemistry of the C-glycosidic ellagitannins, vescalagin and castalagin, has been reinvestigated using computational methods. DFT calculations of their (1)H and (13)C NMR spectra, as well as TDDFT calculations of the ECD spectra of their des-hexahydroxydiphenoyl analogues, revealed that the structure of the triphenoyl moiety of vescalagin and castalagin should be revised.

Bioinspired Total Synthesis of (−)‐Vescalin: A Nonahydroxytriphenoylated C‐Glucosidic Ellagitannin

“…Finally,ah ydrogenolytic debenzylation of b-19,f ollowed by ah ydrolytic release of the 4,6-O-benzylidene group,g ave rise to (À)-vescalin (1)i n4 1% yield (Scheme 4), after purification by preparative reverse-phase HPLC,w hich inevitably occasions some loss of such ap olyphenolic material. All characterization criteria, including circular dichroism data, are in agreement with those of natural 1, [3,4] hence attesting that the penultimate copper(II)/bispidine-mediated coupling step of this synthesis forged its NHTP unit with the correct atropisomerism.…”

“…We opted for aWittig olefination to force the opening of the glucopyranose ring, which is at actic that was successfully employed by the group of Yamada for the conversion from the 4 C 1 to 1 C 4 conformations of glucopyranosic intermediates in their synthesis of the ellagitannin corilagin. [16a, 17] Thus,a fter af ew experiments (see Table S2), the use of the conjugated phosphorane PPh 3 CHCO 2 Et in the presence of 2,2,2-trifluoroethanol (TFE;2equiv) in anhydrous toluene (Vilarrasasc onditions) [18a] was found to efficiently promote the conversion of the cyclic hemiacetal 14 into the expected open-chain olefinic ester (E/Z = 8:2), which was 5-O-galloylated using 11 under Steglich-type conditions to furnish the C-type olefinic ester 15 in 83 % yield from 14.Anosmium-catalyzed dihydroxylation [17,18b,c] of (E)-15,f ollowed by oxidative cleavage of the resulting diol using either Pb(OAc) 4 or PhI(OAc) 2 , [18c] were then performed to afford the B-type liquidambin-like vescalin precursor 16 in 82 %v ersus 62 %yield from 15 (Scheme 3; see details in the Supporting Information).…”

“…(À)-Vescalin (1)i samember of the C-glucosidic ellagitannin subclass of gallic-acid-derived polyphenolic secondary metabolites, [1] which are produced by dicotyledonous plant species of the Angiospermea, and in particular by some of the more highly evolved species belonging to the Rosidae, Hamamelidae,a nd Dilleniidae subclasses (Figure 1). [2] (À)-Vescalin (1)w as first isolated from Quercus (oak) and Castanea (chestnut) species of the Fagaceae family (Hamamelidae), together with its a-epimer (+ +)-castalin (2)and their congeners (À)-vescalagin (3)a nd (À)-castalagin (4). [3] The double axially chiral 2,3,5-O-nonahydroxytriphenoyl (NHTP) unit, also referred to as the flavogallonyl unit, [1b] is the special structural feature of these ellagitannins,w hich are otherwise typified by their glucose core in an open-chain form and their C-arylglucosidic bond.…”

Structural Revisions in Natural Ellagitannins

“…In accordance with the correction, the C-1 stereochemistries of castalin, vescalin, castalagin, and vescalagin were revised, resulting in their third structures. Twenty-five years later, in 2015, Tanaka corrected the axial chirality of the NHTP group and revised the structures of castalin and vescalin to be (1 R ,a S ,a R )- 89 and (1 S ,a S ,a R )- 89 , respectively [ 82 ]. Consequently, the structures of castalagin and vescalagin were revised, resulting in the latest structures.…”

“…In the correction of the axial chirality of the NHTP group in 2015, chemical calculations were utilized [ 82 ]. Using the density functional theory (DFT) method, Tanaka calculated each electronic circular dichroism (ECD) spectrum of four isomers of the castalin/vescalin 89 ( Figure 38 ), in which the C-1 stereochemistry and the axial chirality of the NHTP group differed.…”