www.elsevier.nl/locate/carres Carbohydrate Research 330 (2001) 459 – 468 Synthesis and antiperoxidant activity of new phenolic O -glycosides Fabio Ponticelli, a, * Antoaneta Trendafilova, a,1 Massimo Valoti, b Simona Saponara, b GianPietro Sgaragli b a Institute of Organic Chemistry, Uniersity of Siena, I -53100 Siena, Italy b Institute of Pharmacological Sciences, Uniersity of Siena, 53100 Siena, Italy Received 23 October 2000; received in revised form 10 November 2000; accepted 1 December 2000 Abstract We describe the synthesis of some 3-tert -butyl-4-hydroxyphenyl D-glycopyranosides by reaction of tert -butylhy- droquinone with -D-pentaacetyl-glucose, -D-pentaacetyl-galactose, 2-acetamido- and 3,4,6-tri-O -acetyl-2-bu- tanamido-2-deoxy--D-glucopyranosyl chlorides as well as the formation of anomeric 3-tert -butyl-4-hydroxyphenyl 4,6-di-O -acetyl-2,3-dideoxy-D-erythro -hex-2-eno-pyranosides by reaction between tert -butylhydroquinone and 3,4,6- tri-O -acetyl-D-glucal. All compounds, except 3-tert -butyl-4-hydroxyphenyl - and -D-glucopyranosides, inhibited lipid peroxidation with a degree of potency comparable to that of tert -butyl hydroxyanisole. © 2001 Elsevier Science Ltd. All rights reserved. Keywords: Antioxidants; O-Glycosylated tert -butylhydroquinones; Glucals; Inhibition of lipid peroxidation 1. Introduction It is well established that phenols, in their capacity as hydrogen donors, react with lipid radicals 1 and form stable phenoxy radicals, therefore being effective chain breaking an- tioxidants. 2 Phenol itself is inactive as an an- tioxidant, but substitution of alkyl groups into the ortho or para position increases the elec- tron density on the hydroxyl group by an inductive effect and thus increases its reactiv- ity with lipid radicals. 3 tert -Butyl hydroxyan- isole (BHA) is a synthetic phenolic antioxidant widely used as a stabiliser for fats, oils and lipid-containing foods. 4 Recently, Sgaragli et al. 5 have reported that some hin- dered phenols like BHA exhibit both antispas- mogenic and antioxidant activity. It was proposed that these two potentially useful properties could be combined in properly functionalised phenols and might thus be ef- fective drugs in the prevention of tissue dam- age from ischemia-reperfusion injury. 6 We previously have synthesised 7 a series of BHA analogues with different water solubility and/ or modified antioxidant properties in order to verify their activity either in the extracellular or in the intracellular environment. In the present study tert -butylhydroquinone (BHQ) (1), selected as a suitable target compound, was O -glycosylated with different sugars (D- glucose, D-galactose, D-glucosamine, D-glu- cal). The difficulties in the preparation of glycosides of a diphenol, such as BHQ, arise * Corresponding author. E -mail address: ponticelli@unisi.it (F. Ponticelli). 1 Present address: Institute of Organic Chemistry with Cen- tre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria. 0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:S0008-6215(00)00313-X