Jan P. Steynberg

Conformation and Complexation of Tannins: NMR Spectra and Molecular Search Modeling of Flavan-3-ols

Studies of flavan‐3‐ols in their biologically significant phenolic form show that both H‐6 and C‐6 resonances are downfield from H‐8 and C‐8. Therefore, assignments for the H atoms of the A‐ring are inverse to those commonly reported. By contrast, in the methyl ether and methyl ether acetate derivatives, both H‐8 and C‐8 are downfield from H‐6 and C‐6 and assignments commonly reported for C‐6 and C‐8 are incorrect. The assignments commonly reported for the peracetate derivatives are correct. In contrast to results observed for dimeric flavans, solvent effects on chemical shifts and coupling constants are small in monomeric flavan derivatives. The small heterocyclic ring J2,3 coupling constants of 2,3‐cis‐flavans can be defined by lineshape analysis of H‐3. These results provide the first evidence for the conformations of the common 2,3‐cis‐flavans in solution. With the exception of compounds carrying a bulky acetate at C‐3, a GMMX global search protocol provides reasonable predictions of heterocyclic ring coupling constants.

Oligomeric flavanoids. Part W. base-catalyzed pyran rearrangements of procyanidin B-2, and evidence for the oxidative transformation of B- to A-type procyanidins☆

Abstract Procyanidin B-2 3 is subject to facile C-ring isomerizations in 0.1M NaHCO3 solution to form a novel series of 3,4,9, 10-tetrahydro-2H, 8-pyrano[2,3-h]chromenes 7 , 9 , and 10 . The low percentage conversion of B- to A-type procyanidin 2 is rationalized in terms of an initial oxidative removal of hydride ion at C-2 (C-ring).

Phlobatannins, a novel class of ring-isomerized condensed tannins

Four members of a novel class of natural ‘phlobaphene’ condensed tannins, representing the products of stereospecific ring-isomerization of those 2,3-trans-3,4-trans-(–)-fisetinidol units present in ‘conventional’[4,8]-bi-and [4,6:4,8]-tri-flavanoid profisetinidins, are defined as functionalized 8,9-trans-9,10-cis-3,4,9,10-tetrahydro-2H,8H-pyrano[2,3-h]chromene (1) and the homologous hexahydrodipyrano[2,3-f,2′,3′-h]chromene (5) by nuclear Overhauser effect difference spectrometry.

Oligomeric flavanoids. Part 3. Structure and synthesis of phlobatannins related to (–)-fisetinidol-(4α,6)- and (4α,8)-(+)-catechin profisetinidins

Several members of the novel class of natural ‘phlobaphene’ condensed tannins, representing the products of c-ring isomerization of 2,3-trans-3,4-trans-(–)-fisetinidol units present in (4,6)- and (4,8)-biflavanoid profisetinidins, have been characterized by 1H n.m.r. n.o.e. difference spectroscopy. These include the functionalized 8,9-trans-9,1 0-cis-tetrahydropyrano[2,3-h]chromenes (9) and (12), and the [2,3-f]- and [2,3-g] regioisomers (14) and (19). Since the (4α,8)-biflavanoid (1) is subject to extensive base-catalysed rearrangement and epimerization, the protected 4-O-methyl ethers (E-ring)(2) and (6) were utilized to confirm the proposed structures of phlobatannins by stereospecific C-ring isomerization of (2) and (6) under basic conditions.

The first condensed tannins based on a stilbene

Abstract In addition to ‘conventional” proguibourtinidin condensed tannins, Rhodesian copalwood (Guibourtia coleosperma) contains significant concentrations of bi- and triflavanoid analogues uniquely based on nucleophilic trans-3,3′,4′,5-tetrahydroxystilbene and potentially electrophilic 2,3-cis- and 2,3-trans-4′,7-dihydroxyflavan-3,4-diols (leucoguibourtinidins).

Oligomeric flavanoids. Part 18. Dimeric prorobinetinidins from Robinia pseudacacia

Abstract The range of naturally occurring prorobinetinidins is extended by characterization of the novel robinetinidol-leucorobinetinidins 3, 5, 7, and 9, the robinetinidol-dihydrorobinetins 11, 13, and 15, a robinetinidol-robinetin 17, and a robinetinidol-flavone analogue 19. The diversity regarding the oxidation level of the chain terminating moieties suggests that the biflavanoids in Robinia pseudacacia may be interrelated via oxidation/reduction of these units. The conspicuous absence of the effects of dynamic rotational isomerism about the interflavanyl bond in the 1H NMR spectra of some of the derivatives is explained in terms of a preferred conformation of this bond rather than to ‘free rotation’.

Condensed tannins: A novel rearrangement of procyanidins and prodelphinidins in thiolytic cleavage

Abstract Conditions commonly used for the thiolytic cleavage of interflavanoid bonds of condensed tannins also result in cleavage of the C4 to C10 bond of flavan units. Subsequent electrophilic attack of the C4 carbocation on the C2′ or C6′ of the B-ring, and loss of phloroglucinol (the A-ring), result in the formation of a mixture of 1,3- dithiobenzyl-2,4,5,6-tetrahydroxy indane diastereomers.

Absolute configurations of flavan-3-ols and 4-arylflavan-3-olsvia a modified mosher's method

Abstract 1 H NMR Analysis of R-(+)-α-methoxy-α-trifluoromethylphenyl acetic acid (MTPA) esters of different sets of enantiomeric flavan-3-ols and 4-arylflavan-3-ols respectively, permits assessment of the absolute configurations at C-3 of these condensed tannin structural units.

Oligomeric flavanoids. Part 16. Novel prorobinetinidins and the first A-type proanthocyanidin with a 5-deoxy A- and a 3,4-cis C-ring from the maiden investigation of commercial wattle bark extract

Structural examination of the phenolic metabolites of commercially used wattle bark extract reveals the presence of a range of novel flavanoids comprising (–)-epirobinetinidol 1, the first C-methyl proanthocyanidin, (–)-fisetinidol-(4α,8)-6-methyl-(+)-catechin 3, the first prorobinetinidins with 3,4-cis C-ring configurations 7 and 9, and the unique A-type prorobinetinidin 11 representing the first entry amongst this class of oligoflavanoids exhibiting a 5-deoxy A- and a 3,4-cis C-ring. They are accompanied by a range of functionalized prorobinetinidin -type tetrahydropyrano[2,3-f]chromenes 20, 23, 25 and 28 and the trimeric ‘isomerization-intermediate’32, all exhibiting the characteristic structural features that are essential for the use of ‘Mimosa’ extract in cold-setting adhesives and leather-tanning applications. In addition, evidence demonstrating that the dynamic A-E conformational equilibrium of flavan-3-ol moieties in condensed tannins may be influenced by external factors is presented.

Oligomeric flavanoids. Part 4. Base-catalysed conversions of (–)-fisetinidol-(+)-catechin profisetinidins with 2,3-trans-3,4-cis-flavan-3-ol constituent units

Additional novel members of the class of natural ‘phlobaphene’ condensed tannins, representing the products of C-ring isomerization of 2,3-trans-3,4-cis-(–)-fisetinidol units present in (4β,6)- and (4β,8)-biflavanoid profisetinidins have been characterized. These comprise the functionalized 8,9-trans-9,1 0-trans-3,4,9,10-tetrahydro-2H,8H-pyrano[2,3-h]chromenes (2) and (11), and 8,9-cis-9, 10-trans analogue (8), and a 6,7-cis-7,8-trans-[2,3-f]-regioisomer (27). Analogues (8) and (11) are prototypes of a unique class of phlobatannins in which the resorcinol A- and pyrocatechol B-rings are interchanged relative to their positions in the more common isomers. Their formation represents a novel rearrangement of profisetinidins with 2,3-trans-3,4-cis-flavan-3-ol units, e.g. (1) with concomitant inversion of absolute configuration at 3-C(C), under base catalysis. The proposed structures of the natural products were confirmed by synthesis via base-catalysed conversion of (–)-fisetinidol-(4β,8)- and (4β,6)-(+)-catechin O-methyl ethers (1) and (14).