S. Benetti, C. De Risi, G. Pollini
Jan 25, 2012
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0
Influential Citations
78
Citations
Quality indicators
Journal
Chemical reviews
Abstract
Natural and man-made organosulfur compounds play important roles in biological and medicinal chemistry. Among the various classes of organic sulfur compounds, dihydroand especially tetrahydrothiophenes have attracted particular attention because of the widespread occurrence as ring system motifs in natural and nonnatural products displaying a broad spectrum of biological activities. Tetrahydrothiophene-based compounds include the essential coenzyme biotin 1, a water-soluble vitamin involved in important biological functions, and the potent α-glucosidase inhibitors salacinol 2 6 and kotalanol 3, isolated from several Salacia plant species. Recently, the related compounds salaprinol 4 and ponkoranol 5 were isolated from Salacia prinoides, and significant efforts to prepare these cyclic sulfonium salts and synthetic analogues, including 6 and 7, have been made in the past few years (Figure 1). Further representative compounds are the 40-thioadenosine derivative 8, a highly potent and selective A3 adenosine receptor antagonist; the 40-thiocytidine nucleoside 9, active against HSV-1 and HSV-2; the cholecystokinin type-B receptor antagonist tetronothiodin 10; and (R)-tetrahydrothiophen-3-ol 11, 18 a pivotal intermediate to obtain the potent antibacterial Sulopenem 12 (Figure 2). The field of applications of tetrahydrothiophenes is impressively wide in scope: these compounds have been employed as templates to assist and control various chemical transformations, including asymmetric hydrogenation, catalytic asymmetric epoxidation, and catalytic intramolecular cyclopropanation. Moreover, adsorption of tetrahydrothiophene on gold has emerged as a powerful tool to obtain self-assembled monolayers (SAMs), which can be used to control physical and chemical properties of surfaces for various technological purposes. The dihydrothiophene ring system is a common structural feature of many bioactive compounds, some of which are shown in Figure 3. In particular, (S)-ethyl 4-amino-4,5-dihydrothiophene-2-carboxylate 13 inhibits copper amine oxidases (CAOs), the unnatural L-nucleoside 14 displays potent anti-HIV activity without significant toxicity, and 4,5-dihydrothiophene-3-carbonitrile 15 exhibits antibacterial and antifungal properties. Interestingly, it has been demonstrated that calicheamicin becomes active Figure 1.