The constitution of oligomeric benzofuranoids

[摘要] English: Berchemia zeyheri is known for its unique red heartwood, a property that was probablyresponsible for the first phytochemical investigation into the flavonoid content of this tree.The heartwood contains a unique series of biflavonoids with one of more benzofuranoidmoieties. These are usually found in diastereomeric mixtures, the biogenetic origin andstereochemistry of which have hitherto been unknown. This investigation thus representsa renewed effort to solve some of the intricate problems associated with these compounds.The high concentration of maesopsin in the heartwood made extensive enrichment andfractionation by the use of Craig countercurrent distribution techniques and Sephadex LH-20 gelchromatography necessary. The two diastereomers of 4',5, 7-tri-O-methylnaringenin-(3a~ 7)-2,4,4',6-tetra-Omethylmaesopsinwere, for the first time, successfully isolated and separated. Reductionof these diastereomers with Na(CN)BH3 gave two enantiomeric pure fragments. Theconformations of the heterocyclic rings of these fragments were established by molecularmechanics (MMX and GMMX) and semi-empirical methods (AMI). These resultsallowed the absolute configuration of the fragments to be deduced from CD-curves of thecompounds by application of Snatzke's rule for a,~-unsaturated five-membered cyclicrings. A n.O.e. correlation observed for one of the diastereomers only, correlates thestereocenter of the maesopsin moiety, of known absolute configuration, with a specificconfiguration of the naringenin unit, thus defining the absolute configuration of the dimer.These results also allowed the determination of the absolute stereochemistry of two regioisomersof the above dimers, 4',5, 7-tri-O-methylnaringenin-(3a~5)-2,4,4',6-tetra-Omethylmaesopsinand its epimer. The 13CNMR spectra of these related dimers were alsostudied and fully elucidated by means of HMQC and HMBC experiments. The structureand stereochemistry of two novel isoflavanone-benzofuranone biflavonoids, 4',5,7-tri-Omethyldihydrogenistein-fêcc-» 7)-2,4,4',6-tetra-O-methylmaesopsin and its epirner, weresimilarly determined.Resolution of maesopsin, the main metabolite in the heartwood, by means of HPLC using a chiral column, for the first time gave access to the two enantiomers of thisbenzofuranoid.4,4',6- Tri-O-methyl-2-deoxymaesopsin-(2~ 7)-2,4,4',6-tetra-O-methyl-maesopsin and itsepimer, consist of two benzofuranoid constituent units. An X-ray crystal structure wasobtained for the one diastereomer, but due to the presence of a symmetric Pbea pointgroup, only the relative configuration could be determined. After the racemic nature ofeach of the diastereomers was determined, each epimer was resolved with HPLC into itsconstituent enantiomers. The information obtained from the CD curves and crystalstructure allowed the determination of the absolute stereochemistry of each of theenantiomers.Four further epimeric biflavonoids were isolated as the hepta-O-methyl ethers. Evidenceobtained from 13C NMR data suggested the presence of a y-lactone functionality in theupper benzofuranoid moiety, identifying the dimers as the epimers of 4,6-dimethoxy-3-( 4-methoxy-benzyl)benzo[b ]furan-2(3H)-one-(2~5)-2,4,4',6-tetra-O-methylmaesopsin andthe (2~ 7)-coupled regio-isomer.In order to supplement the above data, an asymmetric synthesis of maesopsin wasattempted. The first attempt involved the oxidation of 2-( 4-methoxybenzyl)-4,6-dimethoxybenzo[b ]furan-3(2H)-one, obtained by reduction of the corresponding aurone,with AD-mix-a, a stereoselective catalyst, or chiral oxaziridine. The former afforded thedesired product in low yield but no stereo selectivity while the latter method realized amuch-improved yield, but still with no selectivity. This lack of selectivity is attributed toequilibrium of the product with the a-diketone. Attempts to prevent the formation of thisequilibrium product were unsuccessful. A second synthetic attempt involved benzylationof 2,4,6-trimethoxybenzo[b]furan-3-(2H)-one with (-)-sparteine as chiral auxiliary, butagain resulted in high yields but no stereo selectivity.

[发布机构] University of the Free State