Synthesis and analysis of Eriosema isoflavonoids and derivatives thereof.
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Date
2011
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Abstract
Kraussianone 1 and kraussianone 2 were previously isolated as active compounds from the roots of Eriosema kraussianum Meisn., a plant used for the treatment of male impotence and urinary complaints in KwaZulu-Natal. The objectives of this study were firstly, to develop a method for the analysis of metabolites from E. kraussianum and other Eriosema plants that are used for erectile dysfunction and secondly, to develop synthetic methods for
kraussianone 1 and structurally related compounds.
A reversed-phase HPLC-PDA method was developed for the analysis of the extracts of plants from different sources, two of which were authentic E. kraussianum collected from the Drakensberg and Pietermaritzburg. The roots of other Eriosema species called ubangalala and uqonsi in Isizulu were also analysed. These plants were bought from the local herbal traders. The extracts of the two E. kraussianum plants and one uqonsi sample
showed a similar chemical profile, even though there were variations in the relative concentrations of the metabolites within each plant. In these three plants, kraussianone 1, the most active metabolite of E. kraussianum, occurred in relatively low quantities, whereas kraussianone 2 was one of the major constituents. The other commercial plants that were analysed contained different compounds from those found in E. kraussianum.
The HPLC method developed herein facilitates rapid identification and relative quantification of metabolites from E. kraussianum.
Strategies based on semi-synthesis and total synthesis were employed for the preparation of kraussianone 1. The semi-synthetic route was based on the transformation of the prenyl side chain of kraussianone 2 into a linear dimethylpyran scaffold fused to the A-ring. Two routes were investigated for the semi-synthesis of kraussianone 1 from kraussianone 2. In
the first route, the dimethylchromene ring was to be prepared by the acid-catalysed cyclisation of the prenyl group of kraussianone 2, followed by dehydrogenation of the resulting dimethylchroman chromophore. This route was abandoned due to poor regioselectivity of the cyclisation reaction and the difficulty of oxidising the dimethylchroman scaffold on the phloroglucinol moiety into a dimethylchromene. The second strategy involved selective protection of the OH-2', followed by DDQ-mediated oxidative cyclisation of the prenyl group to OH-7. This was the most viable route and
kraussianone 1 was prepared in an overall yield of 54% from kraussianone 2.
The total synthesis of kraussianone 1, on the other hand, employed the Suzuki-Miyaura reaction for the construction of the isoflavone nucleus and the regioselective introduction of the dimethylpyran scaffolds to the A- and B-rings. The key precursors in this synthesis were 3-iodo-5,7-dimethoxymethoxychromone and a boronic acid coupling partner, 7-
benzyloxy-2,2-dimethylchromene-6-boronic acid, already bearing the prerequisite chromene scaffold attached to the B-ring. The isoflavones genistein, 2-hydroxygenistein, eriosemaone D and a geranyl analogue of kraussianone 1 were prepared via the route developed for the total synthesis of kraussianone 1 by structural modifications of rings A and B. Furthermore, this synthetic approach was expanded to the synthesis of the
coumarochromones lupinalbin A and lupinalbin H. The development of the feasible semi-synthetic and total synthetic routes described herein
for kraussianone 1 is of importance for the production of material for an in depth study of the pharmacological activities and the structure-activity relationship studies of kraussianone 1 and related compounds.
Description
Thesis (Ph.D.)-University of KwaZulu-Natal, 2011.
Keywords
Theses--Chemistry., Flavonoids., Medicinal plants., Eriosema.