Epimesquitol-flavone dimers and related oligomers from Acacia nigrescens synthesis of 3',4',7,8-substituted flavonoid monomers

English: The previous investigation, by Fourie in the 1970's, revealed the presence of phenolic compounds in the heartwood of Knobwood (Acacia nigrescens), comprising a series of leucomelacacinidins. Early suggestions that oligomers containing the pyrogallol-type Aring moieties are unlikely to exist, prompted a detailed reinvestigation for possible higher oligomers in the heartwood of this tree. A number of promelacacinidin dimers were discovered. Enrichment of the heartwood extract followed by a number of gel separations resulted in complex phenolic mixtures of dimeric- and polymeric material. The purification of which was facilitated by derivatization of the phenolic compounds to methylether acetates. Structural elucidation of the compounds was carried out with the utilization of mass speetrometry and detailed ¹H NMR spectroscopy (300 MHz), ¹³C, COSY, NOESY, HMQC and HMBC experiments on the methylether acetate derivatives. Apart from the presence of epimesquitol-4α-ol, epimesquitol-4β-ol, dihidroflavonol, flavonol (melanoxetin) and the flavanone in the heartwood of A. nigreseens it also afforded a variety of C-C linked dimeric promelacacinidins. Two C-4 (C-ring) —› C-6 (D-ring) linked dimers, epimesquitol-( 4β —›6)-epimesquitol-4α-ol and epimesquitol-( 4β —›6)- epimesquitol-4β-ol were isolated from this tree. The unique class of proanthocyanidins with a C-4 (C-ring) —›C-5 (D-ring) linkage was extended by the present isolation of mesquitol-(4α —›5)-epimesquitol-4β-ol and the two novel promelacacinidin dimers, mesquitol- (4 α—›5)-3,3' ,4' ,7,8-pentahydroxy flavonone and epimesquitol-( 4β —›5)-3,3',4' ,7,8-pentahydroxy flavonone. The novel promelacacinidin dimer, with a unique C-4 (C-ring) —›C-3 (D-ring) interflavanyl linkage e.g. ent-epimesquitol-( 4α—›3)-3',4', 7,8-tetrahydroxyflavanone was also isolated and the structure elucidated. Unlike previous studies, the synthetic approach where epimesquitol-4β-thiobenzylether was used with epimesquitol-4α-ol as nucleophile and AgBF4 as thiophylic Lewis acid, no dimeric promelacacinidins were isolated. This prompted the alternative use of DMTSF as initiator for nucleophilic substitution and indeed a C-O-C-linked promelacacinidin was isolated, but not enough material was available for structural elucidation. There is a great deal of uncertainty concerning the general pathway in flavanoid biosyntheses. It was suggested that flav-3-en-3-ols could be key intermediates in this pathway. During previous studies, flav-3-en-3-ols was synthesized in high yield. This encouraged a further investigation as to the reactions of the keto tautomer of the flav-3-en-3-ol, namely the flavan-3-one. A series of successfully oxidations and reductions were carried out on the flavan-3-one, in order to synthesize the flavonol and mesquitol (flavan- 3-ol) for future use in synthesis.