Synthesis, conformation analysis, and characterization of physiologically important flavonoids and isoflavonoids

[摘要] This work contains two parts of study: Synthesis of a series of homoisoflavonoid analogues inorder to investigate a difference between 6- and 8- homoisoflavanone which isolated from ScillaNatalensis and Part II contains conformational analysis of C-ring substituted flavans andanalogues.While the novel homoisoflavanone isolated from Scilla natalensis as the peracetate hasunambiguously been proven by synthesis to have the 5,7,4'-triacetoxy-8-methoxy structureduring this investigation. The control of the substituents (protecting groups) is determined the Aringof a homoisoflavanone which has also been pointed out that great care should be taken in theassignment of the structures of these compound by comparison of proton chemical shifts. This isespecially true when a single methoxy group is situated on a trioxygenated A-ring as there mightnot be an nOe association between the methyl protons and any aromatic hydrogen. The situationmay further be aggravated by the fact that natural products may be isolated as derivatives, likeperacetates, of the naturally occurring free phenolic analogues due to separation difficulties.Although only two of the possible 6 A-ring trioxygenated homoisoflavanones have beensynthesised e.g. 5,7,4'-trihydroxy-6-methoxyhomoisoflavanone and 5,7,4'-trihydroxy-8-methoxyhomoisoflavanone, it is envisaged that the remaining four compounds will also beprepared so the 1H and 13C NMR data of all these compounds both as free phenols andperacetates can be reported. This will be a valuable tool to assist researchers during the isolationand structure elucidation of this class of natural product during future phytochemicalinvestigations.In an effort to divulge the effect of the individual stereocenters form each other, and thus thecombined effet obtained by ECD, it was decided to investigate the chromophore based method ofVCD as measurement of absolute configuration at the different stereogenic centres. If acorrelation between the IR absorption band(s) at certain wave numbers and a specificchromophore in a molecule could be established, it should, in principle, be possible to define theabsolute comfiguration at that point in the molecule by VCD. In order to find a possiblerelationship between chromophores and IR absorption bands in flavonoids and related molecules, a molecular modelling study to determine the preferred conformation of the heterocyclic ring ofthese compounds as well as establish a possible correlation between the chromophore present inthe molecule and IR band(s) was embarked upon. In this regard, the preferred conformation(s) ofthe series of heterocyclic molecules with increasing order of complexity, i.e. no substituent tothree heterocyclic substituents, were determined and correlated with the respective modelled IRfrequencies as well as the experimental absorption bands in the IR spectrum.In this study a complete conformational surface of oxane, chromane, flavan, flavan-3-ols, 4-arylflavan and 4-arylflavan-3-ols is presented to give the global and local minima which reultedin finding the most stable conformations. However, the most stable conformations for thesecompounds are the chair, 2,5-twisted boat and 1,4-twisted boat (oxane); half chair (chromane);[(2R)-equatorial and (2S)-equatorial (flavan)]; [(2S)-equatorial, (3S)-axial and (2S)-equatorial,(3R)-equatorial (flavan-3-ol)]; [(2S)-equatorial, (4R)-axial and (2S)-equatorial, (4S)-equatorial(4-arylflavan)] and {[(2S)-axial, (3S)-equatorial, (4R)-axial], [(2S)-axial, (3S)-equatorial,(4S)-equatorial], [(2S)-equatorial, (3R)-equatorial, (4R)-equatorial] and [(2S)-equatorial,(3R)-equatorial, (4S)-axial] (4-arylflavan-3-ols)}. The assignment of IR absorption fromtheoretical spectra is presented and the excellent match between theoretical and experimental IRanalysis is achieved. It's evidently concluded that the method of using TDDFT calculationstogether with infrared spectroscopy to determine the most stable or preferred conformation wasachieved for flavonoid compounds. The determining of absolute configuration at a chiral centrein selected flavonoid compounds and understanding of its IR spectra is currently underinvestigation with the same approach.The calculated VCD spectrums of the highest populated conformations are presented e.g. [(2R)-equatorial (flavan)]; [(2S)-equatorial, (3S)-axial and (2S)-equatorial, (3R)-equatorial (flavan-3-ol)]; [(2S)-equatorial, (4R)-axial and (2S)-equatorial, (4S)-equatorial (4-arylflavan)] and {[(2S)-axial, (3S)-equatorial, (4R)-axial], [(2S)-axial, (3S)-equatorial, (4S)-equatorial], [(2S)-equatorial, (3R)-equatorial, (4R)-equatorial] and [(2S)-equatorial, (3R)-equatorial, (4S)-axial](4-arylflavan-3-ols)} were also achieved successfully.

[发布机构] University of the Free State