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Synthesis of seleno-carbohydrates derived from D-galactose
Hugo C. Braga, Ana D. Wouters, Felipe B. Zerillo, Diogo S. Lüdtke ⇑Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, USP, CEP, 05508-900 São Paulo, SP, Brazil
a r t i c l e i n f o
Received 23 July 2010
Received in revised form 26 August 2010
Accepted 29 August 2010
Available online 21 September 2010
Keywords: Galactopyranosides Selenium
a b s t r a c t
The synthesis ofseleno-galactopyranosides in a short and efﬁcient manner is described, starting from the parent carbohydrate D-galactose. The approach described allows the synthesis of small libraries of com- pounds with a number of structural variations at the group attached to selenium. Compounds with aryl, propargyl, allyl, acyl, and alkyl substituents are described.
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Selenium is an essential biological element and it is present in several enzymes, such as glutathione peroxidase (GPx), thioredoxin reductase (TrxR), and formate dehydrogenase.1–5 It is known that the selenium atom plays a key role in the mode of action of such pro- teins, which cannot be played by its closest relative, sulfur.6 Sele-nium has been shown to be involved in a number of important biological processes ranging from cancer prevention,7,8 redox regu- lation,9 aging,10 and immunology to male reproduction.11–13
In light of the important biological activities of selenium com- pounds, the incorporation of selenium into small organic molecules has received much attention in recent years. Thetoxicology and pharmacology of these compounds, as well as their ability to mimic the catalytic behavior of natural enzymes, have been widely stud- ied.14–17 Nevertheless, efﬁcient methods for the incorporation of selenium atoms into carbohydrate frameworks are still limited, de- spite the interesting synthetic and biological potential of carbohy- drates containing selenium in theirstructures.18–22 Examples already reported in the literature show that seleno-carbohydrates are effective depigmenting compounds, inhibiting melanin synthe- sis in melan-A cells, in similar levels to phenylthiourea, which is a well-known inhibitor of such a process.23 In addition, selenosugars have also been detected in human urine as a metabolite for the excretion of selenium.24The incorporation of selenium into nucleo- sides has also been accomplished and the seleno-nucleosides have been found to display important biological proﬁles, including activ- ities against HIV-1 (human immunodeﬁciency virus type-1) and
⇑ Corresponding author. Tel.: +55 11 3091 3687; fax: +55 11 3815 4418.
E-mail address: firstname.lastname@example.org (D.S. Lüdtke).
HBV (hepatitis B virus)2.25,26 Moreover, the replacement of an oxy-
gen atom by selenium, in the nucleoside framework served as an anomalous scattering center, thus facilitating the 3-dimensional structure determination of nucleic acids by X-ray crystallography experiments.27–31
From the synthetic point of view, carbohydrates presenting an organoselenium group at the anomeric position have been describedto act as selective glycosylating agents in the synthesis of oligosaccha- rides,32–34 and as useful intermediates for the synthesis of functional- ized glycals,35 C-glycosides,36 and glycoconjugates.37 In this context, we recently described an easy, straightforward synthetic route for the preparation of a series of chiral seleno-xylofuranosides, starting from the readily available...