Desmond A. Young

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).

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.

Synthesis of condensed tannins. Part 19. Phenol oxidative coupling of (+)-catechin and (+)-mesquitol. Conformation of bis-(+)-catechins

Phenol oxidative coupling of (2R,3S)-2,3-trans-3′,4′,5,7-tetrahydroxyflavan-3-ol[(+)-catechin] generates low yields of ether-{[3′O,8]- and [4′O,8]-} and atropisomeric carbon-linked {[2′,8]-,[2′,6]-, and [6′,8]-} bis-(+)-catechins. The isomeric structures were differentiated by nuclear Overhauser effect difference spectroscopy. Extension of condensation of (+)-catechin with (2R,3S)-2,3-trans-3′,4′,7,8-tetrahydroxyflavan-3-ol[(+)-mesquitol] readily affords the four atropisomeric [5,6:5,8]-bis-[(+)-mesquitol]-(+)-catechins previously encountered in the heartwood of Prosopis glandulosa(‘Mesquite’).

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).

Natural (-)-fisetinidol-(4,8)-(-)-epicatechin profisetinidins.

Abstract The natural occurrence of the first profisetinidins associated with (−)-epicatechin is demonstrated in the heartwood of three legumes. 1 H NMR spectroscopy at 300 MHz permits assessment of the relative abundance of the predominant rotamers in each of the heptamethyl ether diacetates of the (−)-fisetinidol-(4α,8) and (4β,8)-(−)-epicatechins at ambient temperatures.

Phlobatannins via facile ring isomerizations of profisetinidin and prorobinetinidin condensed tannin units

[4,8]-2,3-trans-3,4-trans-(–)-Fisetinidol-2,3-trans-(+)-catechin and its (–)-robinetinidol homologue are to a varying degree subject to facile ring isomerizations (also when preceded by induced positional isomerization) in NaHCO3–Na2CO3 buffer solution under nitrogen, with liberation of reactive nucleophilic resorcinol units to form a range of bifunctional phlobatannins.

Profisetinidin-type 4-arylflavan-3-ols and related δ-lactones.

Abstract The natural occurrence of the first profisetinidin-type 4-arylflavan-3-ols, 4α- and 4β-(2,4-dihydroxy-3-methoxyphenyl)-(−)-fisetinidols, and a related δ-lactone, 7,8,9,13-tetrahydroxy-2-(3,4-dihydroxyphenyl)-2,3- trans -3,4- cis -2,3-10-trihydrobenzopyrano[3,4- c ]-2-benzopyran-1-one in the heartwood of Peltophorum africanum is demonstrated. In the heartwood of Burkea africana the δ-lactone is accompanied by its 2-(3,4,5-trihydroxyphenyl)-analogue and the 3- O -galloyl ester of (−)-robinetinidol, the first gallate involving a 5-deoxy flavan-3-ol. The biogenetic implications of the coexistence of these novel metabolites are briefly discussed.

Regio- and stereoselective oxygenation of flavan-s-ol-, 4-arylflavan- 3-ol-, and biflavanoid-derivatives with potassium persulphate

Abstract The phenolic methyl ethers of flavan-3-ols, 4-arylflavan-3-ols, and (-)-fisetinidol-(4,8)-( + )-catechin biflavanoids are susceptible to regio- and stere- oselective hydroxylation at C-4 in moderate to high yields with potassium persul- phate/cupric sulphate in aqueous acetonitrile. The resultant 4-functionalized analogues are of both synthetic and degradative significance in condensed tannin chemistry.

Oligomeric flavanoids. Part 8. The first profisetinidins and proguibourtinidins based on C-8 substituted (–)-fisetinidol units and related C-ring isomerized analogues

Structural examination of the phenolic metabolites of Colophospermum mopane reveals the presence of the first profisetinidins and proguibourtinidins based on C-8 substituted (–)-fisetinidol units i.e. the (4α,8)-bis-(–)-fisetinidol (1), (+)-epifisetinidol-(4α,8)-(–)-fisetinidol (3), and the (+)-guibourtinidol-(4α,8)-(–)-fisetinidol (5). They are accompanied by the related functionalized tetrahydropyrano[2,3-h]chromenes (9), (11), (13), (15), and (17), and by a 2,4-diaryl-6-(2,-benzopyranyl)chroman (19), the first C-ring isomerized analogue derived from a B-ring coupled profisetinidin. Efforts towards the synthesis of the (4,8)-bis-fisetinidols from 6-bromo-(–)-fisetinidol and the appropriate flavan-3,4-diol, lead to the biaryl type biflavanoids (33) and (35). Their genesis is explained in terms of an oxidative substitution reaction initiated by bromonium ion.