Stereoselective Synthesis of Benzylated Prodelphinidins and Their Diastereomers with Use of the Mitsunobu Reaction in the Preparation of Their Gallocatechin Precursors

Abstract

The tetrabenzylated catechin 9 was prepared by benzylation of the commercially available pure (+)‐catechin (3) and coupled with the commercially unavailable pentabenzylated(–)‐gallocatechin 10, prepared in a one‐step Mitsunobu‐type cyclization of the triol 8. The highly stereoselective synthesis of benzylated prodelphinidins – catechin‐(4α→8)‐gallocatechin (13), gallocatechin‐(4α→8)‐gallocatechin (14), and gallocatechin‐(4α→8)‐catechin (15) – is reported for the first time. The ESI(+)‐CID mass spectra of the coupling products were found to feature regioselective retro‐Diels–Alder (RDA) reactions and unusual sequential losses of pairs of C7H7· radicals (182 u) from the Na+ adduct ions.

Recent Syntheses of Proanthocyanidins

“…36 Until now only an example of total synthesis of prodelphinidin B3 (14) and C2 (16) has been reported by Makabe and co-workers using equimolar coupling between nucleophilic and electrophilic partners in the presence of Lewis acid. 5 The gallocatechin-derived building block 88 was constructed as Chan and co-workers reported with slight modification.…”

Syntheses of prodelphinidin B3 and C2, and their antitumor activities through cell cycle arrest and caspase-3 activation

“…28 The 1 H and 13 C NMR spectral data of 10 were in good agreement with the reported values. 29 The 3,4-cis diastereomer was not detected. Finally deprotection of the benzyl ethers of 10 and subsequent lyophilization afforded prodelphinidin B3 (1) in good yield.…”

“…29 Until now no total synthesis of prodelphinidins has been reported. The typical synthesis of catechin derived oligomers can be accomplished using Lewis acid-mediated condensation of catechin nucleophiles and electrophiles.…”

Consecutive losses of two benzyl radicals from the [M + Na]+ adduct ions of di- and tri(benzyloxy)benzenes under ESI/CID conditions

“…Recently, we reported on the synthesis and mass spectrometric characterization of a number of per-O-benzylated polyphenols derived from dimeric gallocatechins (prodelphinidins) [35]. ESI mass spectrometry carried out in conjunction with collisioninduced fragmentation within a Paul ion trap revealed a strikingly favored loss of two benzyl radicals (2 C 7 H 7 , 182 u) from the [M + Na] + adduct ions.…”