Jacobus J. Botha

Synthesis of condensed tannins. Part 4. A direct biomimetic approach to [4,6]- and[4,8]-biflavanoids

The generation of flavanyl-4-carbo-cations from flavan-3,4-diols and their condensation with nucleophilic flavan-3-ols to form [4,6]- and [4,8]-biflavanoids at ambient temperatures and under mildly acidic aqueous conditions apparently simulates the initial step in condensed tannin formation in a number of natural sources. The stereospecificity (or stereoselectivity) of the reaction is conditioned mainly by the 2,3-cis or 2,3-trans stereochemistry of the parent flavan-3,4-diol, but also by the nucleophilicity of the flavan-3-ol, and its regiospecific (or regioselective) course by steric factors arising from variation in substitution of the receptive A-ring of the flavan-3-ol.

Synthesis of condensed tannins. Part 1. Stereoselective and stereospecific syntheses of optically pure 4-arylflavan-3-ols, and assessment of their absolute stereochemistry at C-4 by means of circular dichroism

Stereoselective and also stereospecific condensation at C-4 of flavan-3,4-diols of known absolute configuration with phloroglucinol and resorcinol in acid medium proceeds at ambient temperatures with partial retention of configuration for 2,3-trans-isomers and with inversion for 2,3-cis-analogues. Circular dichroism spectra of the resultant 4-arylflavan-3-ols all exhibit multiple Cotton effects. The sign of high intensity Cotton effects to low wavelength, contributed by aryl chromophores at C-4, may almost invariably be correlated with the absolute configuration at this chiral centre of 2,3-trans-3,4-trans, 2,3-trans-3,4-cis-, and 2,3-cis-3,4-trans-isomers.

Condensed tannins: direct synthesis, structure, and absolute configuration of four biflavonoids from black wattle bark (‘mimosa’) extract

Optically pure (+)-2,3-trans-3,4-trans-flavan-3,3′,4,4′,7-pentaol [(+)-mollisacacidin] and (+)-2,3-trans-flavan-3,3′,4′,5,7-pentaol [(+)-catechin] condense rapidly in 0·1 M HCl to give good yields of 4,8-linked diastereoisomeric biflavonoid proanthocyanidins of all-trans and 2,3-trans-3,4-cis-2,3-trans configurations, and also the 4,6-linked all-trans isomer; c.d. comparison thus enables confirmation of the absolute configurations of three known 4,8-linked all-trans biflavonoids from black wattle bark as 2R,3S,4S–2R,3S, and also identification of a fourth as 2R,3S,4R–2R,3S.

Synthesis of condensed tannins. Part 7. Angular [4,6 : 4,8]-prorobinetinidin triflavanoids from black wattle (‘Mimosa’) bark extract

The triflavanoid fraction from the bark extract of the black wattle (Acacia mearnsii) comprises five angular prorobinetinidins with their constituent robinetinidol units [4,6 : 4,8]-linked to both (+)-catechin and (+)-gallocatechin. Synthetic proof of structure is provided for three bi-[(–)-robinetinidol]-(+)-catechin diastereoisomers. The complete dominance of prorobinetinidins in the higher oligomeric fractions correlates with the faster condensation rate of the parent (+)-leucorobinetinidin with the nucleophilic substrates compared with competing (+)-leucofisetinidin.

Synthesis of condensed tannins. Part 5. The first angular [4,6 : 4,8]-triflavanoids and their natural counterparts

Angular triflavanoids comprising a group of four diastereoisomeric [4,6 : 4,8]-bi-[(–)-fisetinidol]-(+)-catechins with definable absolute configurations (2R,3S,4S- and 2R,3S,4R-2R,3S-2R,3S,4S; 2R,3S,4S- and 2R,3S,4R,2R,3S-2R,3S,4R) result from flavanyl-4-carbocation mediated condensation of (2R,3S,4R)-flavan-3,3′,4,4′,7-pentaol [(+)-mollisacacidin] at C-6 of the (+)-catechin units of all-trans-(2R,3S,4S-2R,3S)-[4,8]-(–)-fisetinidol-(+)–catechin and its 3,4-cis-(2R,3S,4R-2R,3S) diastereoisomer respectively. The natural coexistence of some of the forementioned species of bi- and tri-flavanoids and their precursors indicate a comparable sequence of 4,8 preceding 4,6 condensation with (+)-catechin as common nucleophile.

Condensed tannins. Circular dichroism method of assessing the absolute configuration at C-4 of 4-arylflavan-3-ols, and stereochemistry of their formation from flavan-3,4-diols

Stereoselective condensation at C-4 of flavan-3,4-diols of known absolute configuration with phloroglucinol and resorcinol proceeds at ambient temperatures with either partial or complete retention of configuration for 2,3-trans-isomers and with inversion for 2,3-cis-isomers, phenomena that are considered to be of prime significance in condensed tannin formation; multiple Cotton effects contributed by aryl chromophores at C-4 dominate the c.d. spectra of the resultant 4-aryl-2,3-trans- and 2,3-cis-flavan-3-ols, enabling unambiguous determination of their absolute configurations at this chiral centre.

Condensed tannins: competing nucleophilic centres in biomimetic condensation reactions

Abstract The relative contributions of nucleophilicity and steric hindrance in determining the course of the reaction during the formation of ‘angular’ trif

Synthesis of condensed tannins. Part 6. The sequence of units, coupling positions and absolute configuration of the first linear [4,6 : 4,6]-triflavanoid with terminal 3,4-diol function

The first linear triflavanoid with a terminal 3,4-diol function, (2R,3S,4S : 2′R,3′S,4′R : 2″R,3″S,4″R)-[4,6 : 4,6]-bi-[(–)-fisetinidol]-(+)-mollisacacidin, is associated with a set of four diastereoisomeric biflavanoid homologues, [4,6]-(–)-fisetinidol-(+)-mollisacacidins, in the heartwood of the black wattle tree, Acacia mearnsii. The sequence of units in the triflavanoid and its bonding points have been determined by n.m.r. spectroscopy at 500 MHz using spin-decoupling techniques. The triflavanoid and two biflavanoids with (2R,3S,4S)-2,3-trans-3,4-cis-configurations in their ‘upper’ units, result from the in vitro self-condensation of their putative precursor (2R,3S,4R)-flavan-3,3′,4,4′,7-pentaol[(+)-mollisacacidin], thus permitting definition of their respective absolute configurations.

Condensed tannins: condensation mode and sequence during formation of synthetic and natural triflavonoids

The first synthesis of 4,8:4,6-linked all-trans- and 2,3-trans-3,4-trans: 2′,3′-trans: 2″,3″-trans-3″,4″-cis-bi[(–)-fisetinidol]-(+)-catechins and recognition of their distribution in nature gives an insight into the mode and sequence of condensations leading to such key triflavonoid intermediates during tannin formation; the synthesis taken in conjuction with c.d. spectra established their absolute configurations.