Natural product glycosides provide continuing inspiration for design and development of therapeutic drugs and semi-synthesis often provides adequate means for their improvement. In case of pentacyclic triterpene saponins, which constitute a large and well studied group of higher plant secondary metabolites, both: glycosides and aglycones are of interest as pharmacologically active compounds but availability of well specified individual chemicals from these groups is very low. Escin (aescin; Aescula hippocastanumextract) – a complex mixture of β-amyrine derived oligosaccharide glycosides containing D-glucoronide moiety, enjoys good opinion as a remedy for chronic vessel insufficiency and capillary blood vessel fragility. Unfortunately all data reported in the literature refer to primary hippocastanus extract (HCE) or multicomponent and ill specified secondary materials, which is against scientific principles, including evidence based medicine rules. In order to generate a pool of individual chemical entities for research of their biological activity, we have decided to start with development of a process for isolation and purification of the main escin aglycone – protoescigenin, based on simple technical operations with exclusion of chromatography. Thus, commercial escin has been converted into pure protoescigenin, on a pilot technical scale, by a two step chemical hydrolysis followed by treatment with a mixture of solvents, which allowed to separate other triterpene aglycones. Regioselective derivatization of protoescigenin to a diketal - 3,24:16,21-di-O-isopropylidene derivative, afforded desired starting material, from which dedicated library of new chemical entities, including saponine mimetic glycoconjugates can be obtained, for studies of their individual biological activity profiles [1]. For practical reasons glycoconjugate design is based on chemical ligation (click chemistry) rather than classical glycosylation protocols.
Financial support from POIG.0101.02-14-072/09-00 grant is gratefully acknowledged.
[1] M.M. Gruza et al.,Molecules, 2013; in press
