Petrus J. Steynberg

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.

Bicyclic phosphines as ligands for cobalt-catalysed hydroformylation

A range of tertiary bicyclic phosphine ligands derived from cis, cis-1,5-cyclooctadiene (Phoban family) was studied by batch autoclave reactions during the hydroformylation of a mixture of linear internal decenes using a cobalt catalyst system. Comparative runs were performed with PBu(3) as representative of standard trialkyl phosphine behaviour. The Phoban ligands comprise of a cyclooctyl bicycle with a mixture of the [3.3.1] and [4.2.1] isomers where the third substituent was systematically varied, Phoban-Q (Q = CH(2)CH(3), (CH(2))(4)CH(3), (CH(2))(9)CH(3), (CH(2))(19)CH(3), (CH(2))(3)N(CH(3))(2), C(6)H(11) and C(6)H(5)). An increase in ligand concentration resulted in a decrease in the reaction rate while the selectivity towards the n-alcohol product increased in accordance with a move from more unmodified catalysis to more modified catalysis. Alcohol yields of 77-85% were obtained at rates of 1.8-2.4 h(-1) for highly modified catalysis. Under highly modified conditions the linearity of the alcohol ranges in a narrow band from approximately 85-90% from Phoban-Ph to Phoban-Cy respectively. Hydrogenation of the alkene substrate varied from approximately 9-15% for Phoban-Ph and Phoban-Cy respectively the least and most electron donating derivatives. The two phosphine isomers were separated for Phoban-C(2) and the hydroformylation activity were re-evaluated for each isomer. The less electron donating [4.2.1] isomer required slightly higher ligand concentrations to achieve fully modified catalysis and gave rates and linearities comparable to the [3.3.1] isomer but giving slightly higher yields due to less hydrogenation of the olefin. In comparison, at fully modified conditions, PBu(3) gave a rate of 0.6 h(-1), alcohol yield of 77%, linearity of 81% and 17% hydrogenation. The crystal structures of the cobalt dimers [Co(CO)(3)(Phoban[3.3.1]-C(2))](2), [Co(CO)(3)(Phoban[3.3.1]-C(5))](2), [Co(CO)(3)(Phoban[3.3.1]-C(3)NMe(2))](2), and [Co(CO)(3)(Phoban[3.3.1]-Cy)](2) have been determined and indicated very similar geometries with Co-Co and Co-P bond distances ranging from 2.6526(10)-2.707(3) and 2.1963(8)-2.2074(9) A respectively. The cone angles of the Phoban ligands were calculated from the crystallographic data, according to the Tolman model, and ranges from 159-165 degrees.

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’.

The structure and synthesis of proguibourtinidins from Cassia abbreviata

Abstract An acetone extract of the bark of Cassia abbreviata yielded guibourtinidol-(4β → 8)-epicfzelechin, guibourtinidol-(4α → 8)-epiafzelechin, guibourtinidol-(4α → 8)-catechin, guibourtinidol-(4β → 8)-epicatechin and ent-guibourtinidol-(4β → 8)-epicatechin. The structures of the proguibourtinidin dimers were confirmed by synthesis via mild acid-condensation. Guibourtinidol-(4α → 8)-afzelechin, previously isolated from Acacia leuderitzii, was also synthesized. Another two proguibourtinidol oligomers, namely, guibourtinidol-(4β → 8)-afzelechin and guibourtinidol-(4α → 6)-afzelechin were products of the previous synthesis but neither of them have been reported to date.

Circular Dichroic Properties of Flavan-3-ols

CD data of all four diastereoisomers of the permethylaryl ether 3-O-acetyl derivatives of a series of flavan-3-ols permit assignment of the absolute configuration at the stereocentres of the heterocyclic ring.

The first natural condensed tannins with (−)-catechin ‘terminal’ units

Abstract The functionalized 2,3- trans -8,9- trans -9,10- cis -3,4,9,10-tetrahydro-2 H ,8 H -pyrano[2,3- h ]chromenes 4 and 6 represent the first naturally occurring condensed tannins with (2 S ,3 R )-2,3- trans -(−)-catechin ‘terminal’ moieties; the structure of 4 is unequivocally confirmed by synthesis.

Selective O-methylation of polyhydroxyflavan-3-ols via benzyl carbonates

Abstract The flavan-3-ols (+)-catechin and (−)-epicatechin were selectively transformed to their 3′,4′-di- O -methyl- and 5,7-di- O methyl-ethers respectively via benzyl carbonates. Such a regioselectivity is facilitated by marked differences in the pKa values of the phenolic hydroxyl groups and by the ability of the o -dihydroxy funtionality of the pyrocatechol B-ring to form borate complexes under mild basic conditions.

Oligomeric flavanoids. Part 25. Cleavage of the acetal functionality in A-type proanthocyanidins☆

Abstract The hepta-O-methyl ethers 3 and 4 of procyanidin A-1 1 and A-2 2 are subject to facile cleavage of the acetal functionality with sodium cyanoboranuide in trifluoroacetic acid at 0°C. This straight forward chemical method permits the unambiguous establishment of the absolute configuration of the DEF-flavanyl unit and the D-ring carbon and oxygen atoms that are involved in the double linkage of the A-class proanthocyanidins.

Oligomeric flavanoids. Part 26. Structure and synthesis of the first profisetinidins with epifisetinidol constituent units

The natural occurrence of the first oligomeric profisetinidins with (2R,3R)-2,3-cis-epifisetinidol chain extender units is demonstrated in the bark of Pithecellobium dulce (Guamuchil). Semi-synthesis using the appropriate flavan-3-ol and flavan-3,4-diol precursors permits unequivocal structural and stereochemical assignment of the novel dimeric epifisetinidol-(4β,8)-catechin and epicatechins 16 and 18, the trimeric bis-epifisetinidol-(4β,6:4β ,8)-catechin and epicatechins 33 and 35, the fisetinidol-(4α,8)-catechin-(6,4β)- epifisetinidol 37 and fisetinidol-(4α,8)-epicatechin-(6,4β)- epifisetinidol 39.

Oligomeric flavanoids. Part 19. Reductive cleavage of the interflavanyl bond in proanthocyanidins

The interflavanyl bond in profisetinidins 1, 4 and 6, and methyl ethers 3, 5, 28 and 29 and procyanidins 24 and 26, and their methyl ethers 25 and 27 is readily subject to cleavage with sodium cyanoboranuide in trifluoroacetic acid at 0 °C. This method will contribute significantly to the structure elucidation of the 5-deoxy (A-ring) proanthocyanidins from important commercial sources. Boltzmann-averaged heterocyclic ring coupling constants as determined by a conformational global search routine (GMMX) and NOE difference spectroscopy were used to assign unequivocally the diastereotopic methylene protons in the 1H NMR spectra of flavan-3-ols, a prerequisite for corroboration of the cleavage mechanism.