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Titolo/Abstract/Parole chiave

Towards the first total synthesis of C-arylglucosidic ellagitannins. A biomimetic approach.

Natangelo, Anna (2010) Towards the first total synthesis of C-arylglucosidic ellagitannins. A biomimetic approach. Tesi di Dottorato , Università degli Studi di Ferrara.

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    Abstract

    C-arylglucosidic ellagitannins represent a unique sub-class of hydrolyzable tannins. Polyphenols such these have attracted considerable interest in the past fifteen years because of possible benefits in human health care and prevention of diseases such as carcinogenesis and arteriosclerosis. However, this class of natural product, with such unique structural architectures and potent biological activities, has not yet been fully explored for therapeutic potential. From here our interest in developing a synthetic strategy for generation of these compounds and their analogues with enhanced pharmacological properties. Our synthetic efforts were so focused on the synthesis of 5-O-degalloyl epipunicacortein A (1) as simple structures of this class of natural compounds. C-arylglucosidic ellagitannins constitute a tannin subclass in which a C–C bond links the C-1 atom of an “open-chain” glucose core to the C- 2’ atom of a galloyl-derived unit esterified to the 2-position of the glucose core. Their C-1-linked galloyl-derived unit is either part of a HHDP ester group bridging the 2- and 3-positions of the glucose core. It is possible to identify three key issues that must be addressed in order to accomplish the synthesis of C-arylglucosidic ellagitannins: - Opening of the sugar - C-arylglucosidation reaction - Atroposelective intramolecular biaryl coupling for the HHDP construction In the end of this work we managed to obtain a route to access the C-arylglucosidic ellagitannins. In the meantime an intramolecular atroposelective methodology for the construction of the hexahydroxyterphenolyl unit (HHDP) was developed, inspired to the Yamada’s total synthesis of corilagin. We are confident it could be successfully applied to the NHTP construction. This strategy required the preparation of a precursor featuring a para-protected galloyl units. Our methodology for the C-arylglucosidic bond formation into biomimetic conditions resulted applicable even on differently protected substrates. So a biomimetic route to C-glucosidic ellagitannins have been developed. The introduction of a conveniently protected galloyl unit on the intermediates A gives access to the a product that could be further submitted to an oxidative coupling in the Yamada’s conditions to give, after deprotection, the NHTP-bearing C-arylglucosidic ellagitannin vescalin (17) First galloylation attempts on compound 17 resulted unsatisfactory. Studies are still on going to address this point. At this point of the synthesis it was possible to obtain a first member of the C-arylglucosidic ellagitannin family. The benzylidene cleavage of compound 7 delivered the degalloyl epi-punicacortein A 1 (1). This molecule has not yet isolated form a natural source, but it is reasonable to suppose that its structure corresponds to a natural compound. The hydrolysis of esters is the most frequent modification incurred by ellagitannins so O-5-degalloyl epipunicacortein A could derive from epipunicacortein A as O-5-degalloyl punicacortein A derives from hydrolysis of its precursor punicacortein A.

    Tipologia del documento:Tesi di Dottorato (Tesi di Dottorato)
    Data:6 Aprile 2010
    Relatore:Manfredini, Stefano
    Coordinatore ciclo:Manfredini, Stefano
    Istituzione:Università degli Studi di Ferrara
    Dottorato:XXII Anno 2007 > SCIENZE FARMACEUTICHE
    Struttura:Dipartimento > Scienze farmaceutiche
    Soggetti:Area 03 - Scienze chimiche > CHIM/09 Farmaceutico tecnologico applicativo
    Parole chiave:punicacorteina A, polifenoli, ellagitannini, accoppiamento ossidativo
    Depositato il:22 Lug 2010 07:34

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