Polyphenols from pericopsis elata and synthesis of selected stilbenes

Abstract

English: The bark of Pericopsis elata (Afrormosia elata) is used by the local population of the Democratic Republic of Congo for the treatment of cancer and for external applications because of its weather resistance. Previous phytochemical studies on Pericopsis elata resulted in the isolation of flavonoids, isoflavonoids, chalcones and stilbene monomers. Among these, stilbenes are known to have biological activities such as antioxidants, antifungal, and act as microbial inhibitors. They posses COX-1 and COX-2 inhibitory effects, affect lipid peroxidation, LDL oxidation, and function as phytoalexins among other activities. Prompted by these claims, we conducted an in depth investigation of the heartwood of P. elata by extraction, isolation and structural elucidation of the metabolites. The enrichment and fractionation of monomeric and dimeric constituents were accomplished mainly by Craig countercurrent distribution techniques and Sephadex LH-20 gel chromatography. Pure compounds were obtained by derivatization and preparative thin layer chromatography. Structural elucidation of the phenolics is based mainly on NMR spectroscopic methods (1H NMR, 13C NMR, COSY, NOESY, HMBC and HMQC), Mass spectrometry and synthetic methods.The monomeric compounds isolated during this study comprise the flavanones (naringenin and eriodictyol), the isoflavones (genistein and biochanin A), a dihydrochalcone [(R)-α,4,2',4'-tetraacetoxydihydrochalcone] and a single α- methyldeoxybenzoin (angolensin). Among the stilbene monomers encountered are resveratrol, isorhapontigenin and large amounts of piceatannol. Structures of the dimeric stilbnes isolated apparently originate from different combinations of piceatannol (3,4,3',5'-tetrahydroxystilbene) (the major constituent ~ 16% of the phenolic content of P. elata) and 3,4,3',4'-tetrahydroxystilbene. To the best of our knowledge rel-2,3-trans-2-(3,4-dimethoxyphenyl)-3-(3,5-dimethoxyphenyl)-6-[2-(3,5- dimethoxyphenyl)-E-1-ethenyl]benzodioxane, rel-2,3-trans-2-(3,4-dimethoxyphenyl)-3- (3,4-dimethoxyphenyl)-4-[2-(3,4- dimethoxyphenyl) )-E-1-ethenyl]-6-methoxy-2,3- dihydrobenzofuran, rel-2,3-trans-2-(3,4-diacetoxyphenyl)-3-(3,5-diacetoxyphenyl)-4-[2- (3,4-diacetoxyphenyl) )-E-1-ethenyl]-6-acetoxy-2,3-dihydrobenzofuran, rel-2,3-trans-2- (3,4-dimethoxyphenyl)-3-(3,5-dimethoxyphenyl)-4-[2-(3,5-dimethoxyphenyl) )-Z-1- ethenyl]-6-methoxy-2,3-dihydrobenzofuran, rel-2,3-trans-4-Formyl-2-(3,4- dimethoxyphenyl)-3-(3,5-dimethoxyphenyl)- 6-methoxy-2,3-dihydrobenzofuran and rel- 2,3-trans-2-(3,5-diacetoxyphenyl)-3-(3,5-diacetoxyphenyl)-6-[2-(3,5-diacetoxyphenyl) )- E-1-ethenyl]-4-acetoxy-2,3-dihydrobenzofuran are novel compounds. Structural confirmation of the six novel dimeric stilbenes in particular required definition of structure via synthetic methods. A synthetic approach was thus developed. This protocol comprises the synthesis of piceatannol via the Wittig reaction followed by oxidative coupling of two piceatannols to afford novel dimeric stilbenes. 1H NMR of the methoxy-derivative of synthetic compounds is identical to that of the derivative of two dimeric stilbenes isolated from P. elata.

Afrikaans: Die bas van Pericopsis elata (Afromorsia elata) word deur die inheemse bevolking van die Demokratiese Republiek van die Kongo vir die behandeling van kanker gebruik en, danksy die weerbestandheid daarvan, ook vir eksterne aanwending. Tydens vorige fitochemiese studies van Pericopsis elata is flavonoïede, isoflavonoïede, chalkone en stilbeenmonomere geïsoleer, waar die bewese biologiese aktiwiteite van laasgenoemde antioksidatiewe, antifungale en mikrobiese eienskappe insluit. Stilbene inhibeer COX-1 en COX-2, beïnvloed lipiedperoksidasie, LDL-oksidasie, en tree ook as fitoaleksiene op.Op grond van hierdie aansprake het ons ‘n omvattende ondersoek na die bas van P. elata geloods deur ekstraksie, isolasie en struktuurbepaling van die metaboliete. Die verryking en fraksionering van monomeriese en dimeriese komponente is hoofsaaklik deur Craig teenstroomverspreidingstegnieke en Sephadex LH-20 jel chromatografie bewerkstellig. Suiwer verbindings is ná derivatisering en preparatiewe dunlaagchromatografie geïsoleer. Struktuurbepaling van die fenole berus hoofsaaklik op KMR spektroskopiese metodes (1H KMR, 13C KMR, COSY, NOESY, HMBC en HMQC), massaspektrometrie en sintetiese metodes. Die monomeriese verbindings wat tydens hierdie studie geïsoleer is, sluit die flavanone (naringenien en eriodiktiol), isoflavone (genisteïen en biochanien A) ‘n dihidrochalkoon [(R)-α-?,4,2’,4’-tetra-asetoksidihidrochalkoon] en ‘n enkele α-metieldeoksibensoïen (angolensien), in. Stilbeenmonomere wat geïsoleer is sluit resveratrol, isorapontigenien en groot hoeveelhede pikeatannol in. Die strukture van die dimeriese stilbene wat geïsoleer is, spruit oënskynlik uit verskillende kombinasies van pikeatannol (3,4,3',5'-tetrahidroksistilbeen) (die hoofkomponent ~ 16% van die fenoliese inhoud van P. elata) en 3,4,3',4'- tetrahidroksistilbeen. Sover bekend is rel-2,3-trans-2-(3,4-dimetoksifeniel)-3-(3,5- dimetoksifeniel)-6-[2-(3,5-dimetoksifeniel)-E-1-eteniel]bensodioksaan, rel-2,3-trans-2- (3,4-dimetoksifeniel)-3-(3,4-dimetoksifeniel)-4-[2-(3,4-dimetoksifeniel)-E-1-eteniel]-6- metoksi-2,3-dihidrobensofuraan, rel-2,3-trans-2-(3,4-diasetoksifeniel)-3-(3,5- diasetoksifeniel-4-[2-(3,4-diasetoksifeniel)-E-1-eteniel]-6-asetoksi-2,3- dihidrobensofuraan, rel-2,3-trans-2-(3,4-dimetoksifeniel)-3-(3,5-dimetoksifeniel)-4-[2- (3,5-dimetoksifeniel))-Z-1-eteniel]-6-metoksi-2,3-dihidrobensofuraan, rel-2,3-trans-4- formiel-2-(3,4-dimetoksifeniel)-3-(3,4-dimetoksifeniel)-6-metoksi-2,3- dihidrobensofuraan en rel-2,3-trans-2-(3,5-diasetoksifeniel)-3-(3,5-diasetoksifeniel)-6- [2-(3,5-diasetoksi-feniel)-E-1-eteniel]-4-asetoksi-2,3-dihidrobensofuraan nuwe verbindings. Die bevestiging van die strukture van veral die ses nuwe dimeriese stilbene, het sintese genoodsaak. ‘n Protokol vir sintese is dus ontwikkel. Laasgenoemde behels die sintese van pikeatannol via die Wittig-reaksie, gevolg deur die oksidatiewe koppeling van twee pikeatannole om nuwe dimeriese stilbene. 1H KMR van die metoksi-derivatiewe van gesintetiseerde verbindings is identies aan dié van die derivatiewe van twee dimeriese stilbene geïsoleer uit P. elata.