Reinier J. J. Nel

OLIGOMERIC FLAVANOIDS. PART 27*. INTERFLAVANYL BOND FORMATION IN PROCYANIDINS UNDER NEUTRAL CONDITIONS

Abstract Dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) and silver tetrafluoroborate (AgBF4) activate the C4S bond in the 4-thioethers of flavan-3-ols toward carbon nucleophiles to permit formation of the interflavanyl bond in procyanidins under neutral conditions.

Enantioselective synthesis of flavonoids. Part 51. Poly-oxygenated β-hydroxydihydrochalcones

Abstract Epoxidation of a series of poly-oxygenated chalcones with urea-hydrogen peroxide complex in THF in the presence of DBU and poly-( l )- or -( d )-leucine, followed by TBTH/AIBN catalysed ringopening, afforded β-hydroxydihydrochalcones in moderate to high enantiomeric excess and yield.

Stereoselective synthesis of flavonoids. Part 7. Poly-oxygenated β-hydroxydihydrochalcone derivatives

Abstract Epoxidation of a series of poly-oxygenated chalcones with urea-hydrogen peroxide complex in THF in the presence of DBU and poly-( l )- or -( d )-leucine, followed by TBTH/AIBN catalysed ring opening, afforded β-hydroxydihydrochalcones in moderate to high enantiomeric excess and yield. This represents the first stereoselective route towards this group of flavonoids. Epoxidation of a series of poly-oxygenated chalcones with urea-hydrogen peroxide complex in THF in the presence of DBU andpoly-(L)-or-(D)-leucine, followed by TBTH/AIBN catalysed ring opening, afforded β-hydroxydihydrochalcones in moderate to high enantiomeric excess and yield. This represents the first stereoselective access to this group of flavonoids Download : Download full-size image

The novel flavan-3-ol, (2R, 3S)-guibourtinidol and its diastereomers

Abstract The novel (2 R ,3 S )-guibourtinidol, representing the first flavan-3-ol with 4′,7-dihydroxy phenolic substitution pattern, was identified in the heartwood of Cassia abbreviata . Asymmetric dihydroxylation of ( E )-1-(4′- O -methoxymethylphenyl)-3-(2″,4″-di- O -methoxymethylphenyl)-propene with AD-mix-α or AD-mix-β and subsequent acid-catalyzed cyclization afforded the four free phenolic guibourtinidol diastereomers, essentially enantiopure and in good yield.

Absolute configurations of all four stereoisomers of cryptocaryalactone and deacetyl cryptocaryalactone

Using information available in the literature and correlating this with physical data obtained for cryptocaryalactone stereoisomers isolated from C. myrtifolia and C. wyliei, it has been possible to assign the absolute configurations of the four stereoisomers of the title compound and its deacetyl analogue.

Stereoselective Synthesis of Flavonoids. Part 8. Free Phenolic Flavan-3-ol Diastereoisomers

Asymmetric dihydroxylation of a series of poly-O-methoxymethyl-1,3-diarylpropenes with AD-mix-α or AD-mix-β and subsequent acid-catalyzed cyclization of the intermediate syn-diols permits the first synthetic access to all four diastereoisomers of free phenolic flavan-3-ols in high enantiomeric excess and yield.

Recent Advances in the Chemistry of Proanthocyanidins

The oligo- and polymeric proanthocyanidins represent a major group of phenolic constituents in woody and some herbaceous plants.1,2 These compounds usually originate by coupling at C(4) (C-ring) of an electrophilic flavanyl unit, generated from a flavan-4-ol1 or a flavan-3,4-diol3 (the chain extender units), to a nucleophilic flavanyl moiety, often a flavan-3-ol1,3 (the chain terminating unit). Recent developments were initiated by the numerous industrial applications and by the growing realization that the oligo- and polymeric proanthocyanidins may be credited for the profound health-promoting properties of tea, fruit juices, and red wine. This is mainly due to their in vitro radical scavenging4 or antioxidant5 biological properties, while the polyflavanoids in red wine have recently been implicated in protection against cardiovascular disorders,6 e.g. the “French paradox”.7–9 The realization that many of these effects are closely associated with the intramolecular interactions of the proanthocyanidins with other biomolecules has triggered a substantial research effort towards understanding the chemical dynamics of this complex group of natural products. The most relevant results emanating from these studies constitute the subject of this review. The nomenclature delineated in reference 1 will be consistently used.

Manipulation of Some Crucial Bonds in the Molecular Backbone of Proanthocyanidins and Related Compounds

Recent years have witnessed considerable development toward an understanding of the intricate principles governing the chemistry of oligomeric proanthocyanidins. These developments were initiated by the growing realization of the industrial importance of the proanthocyanidins, which is based upon their interactions with key molecules in the biological domain. Despite the surprisingly limited array of carbon-carbon and carbon-oxygen bonds in the heterocycles of proanthocyanidin oligomers, a rich variety of ingenious protocols aimed at manuevering these bonds in a controlled mode has emerged over the past 10–15 years. These studies blend with the heavy focus on the formation and rupture of the interflavanyl bond(s), which played such a decisive role in the structural elucidation of proanthocyanidin oligomers during the seventies and early eighties. Methodologies to chemically exploit the heterocyclic bonds are highly relevant to progress in the chemistry of these important and intriguing biomolecules and constitute the subject of this review.

Enantioselective Synthesis of Flavonoids: Dihydroflavonols and Flavan-3-ols

The beneficial role of flavonoids in general and of the proanthocyanidins in particular to mankind is increasingly being recognized. In addition to the multitude of industrial applications, the oligo- and polymeric proanthocyanidins are now also credited for the profound health-promoting effects of tea, fruit juices, and red wine. This is mainly due to their in vitro antioxidant or radical scavenging properties, while the polyflavonoids in red wine have recently been implicated in protection against cardiovascular disorders, e.g., the “French paradox”. These observations highlight the need for synthetic access to enantiopure flavonoid monomeric precursors exhibiting the aromatic oxygenation pattern of the constituent flavanyl units of the naturally occurring proanthocyanidins, hence paving the route to synthesize a representative series of these important biomolecules. This review accordingly focuses on methodologies aimed at the stereoselective syntheses of the different sets of the four diastereomers of both the dihydroflavonols and fiavan-3-ols exhibiting characteristic “natural product” phenolic oxygenation patterns.