Regioselective Synthesis of Procyanidin B6, A 4-6-Condensed (+)-Catechin Dimer, by Intramolecular Condensation.

Yusuke Higashino,Taisuke Okamoto,Noriyuki Nakajima,Takashi Kawasaki,Masahiro Hamada,Kazuki Mori,Akiko Saito

doi:10.3390/molecules23010205

Abstract

Proanthocyanidins, also known as condensed tannins or oligomeric flavonoids, are found in many edible plants and exhibit interesting biological activities. Herein, we report a new, simple method for the stereoselective synthesis of procyanidin B6, a (+)-catechin-(4-6)-(+)-catechin dimer, by Lewis acid-catalyzed intramolecular condensation. The 5-O-t-butyldimethylsilyl (TBDMS) group of 5,7,3′4′-tetra-O-TBDMS-(+)-catechin was regioselectively removed using trifluoroacetic acid, leading to the “regio-controlled” synthesis of procyanidin B6. The 5-hydroxyl group of the 7,3′,4′-tri-O-TBDMS-(+)-catechin nucleophile and the 3-hydroxyl group of 5,7,3′,4′-tetra-O-benzylated-(+)-catechin electrophile were connected with an azelaic acid. The subsequent SnCl4-catalyzed intramolecular condensation proceeded smoothly to give the 4-6-condensed catechin dimer. This is the first report on the complete regioselective synthesis of a 4-6-connected oligomer without modifying the 8-position.

Highlights

Proanthocyanidins are a class of polyphenols and are generally referred to as condensed tannins or oligomeric flavonoids
Approach that allows for the stereoselective synthesis of 4-8-condensed (+)-catechin dimers
3,4-cis product 6 [28] (Scheme 1). This intramolecular coupling method could potentially solve the difficulties surrounding the stereoselective synthesis of proanthocyanidins such as 3,4-cis oligomers

Summary

Introduction

Proanthocyanidins are a class of polyphenols and are generally referred to as condensed tannins or oligomeric flavonoids They have attracted a great deal of attention because of their strong antioxidant activity and wide range of interesting biological functions [1,2]. Flavan-3-ol derivatives including proanthocyanidins are converted to various structurally complex secondary polyphenols through chemical reactions that occur during food processing such as drying [11], frozen storage [12], and acidic treatment [13]. These complex and diverse forms make the isolation, structural determination, and evaluation of the biological activities of each compound much more difficult.

Methods

Results

Conclusion