ChemInform Abstract: Recent Synthetic Approaches Toward Non-Anomeric Spiroketals in Natural Products

Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique Fédérale de Lausanne, Batochime, CH-1015 Lausanne, Switzerland.
Molecules (Impact Factor: 2.42). 10/2008; 13(10):2570-600. DOI: 10.3390/molecules13102570
Source: PubMed


Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, including those benefiting from conformational anomeric effects (gauche conformers can be more stable than anti conformers because of a contra-steric stabilizing effect), are obtained easily under acidic conditions that permit acetal heterolysis (formation of tertiary oxycarbenium ion intermediates). The synthesis of less stable stereoisomers requires stereoselective acetal forming reactions that do not permit their equilibration with their most stable stereoisomers or, in the case of suitably substituted derivatives, concomitant reactions generating tricyclic products that quench the less stable spiroketal conformers. Ingenuous approaches have been recently developed for the synthesis of naturally occurring [6,6]- and [5,6]-nonanomeric spiroketals and analogues. The identification of several parameters that can influence the stereochemical outcome of spirocyclization processes has led to seminal improvements in the selective preparation of the non-anomeric isomers that are discussed herein. This review also gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomeric effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dioxy substituted isomers (n > 1). Although models assuming sp3-hybridized oxygen atoms have been very popular (rabbit ears for the two non-bonding electron pairs of oxygen atom), sp2-hybridized oxygen atoms are used to describe the conformational anomeric effect.

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Available from: Pierre Vogel, May 25, 2015
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    • "The pH sensitivity is attributed to the presence of spiroacetal moiety which offers a specific conformational framework for the copolymers. In solution, the electrostatic effects—as hard interactions—intervened during the change of pH, overwhelm the polarizability effect (the hyperconjugation: soft interactions) (Favre et al. 2008; Vila and Mosquera 2007; Trapp et al. 2006). As it is well known, to the acetals with vicinal oxy or other polar substituents, the attractive gauche effects (Zefirov et al. 1978; Juaristi 1979; Juaristi and Antunez 1992; Gil et al. 1995; Sasanuma and Sugita 2006) contribute to the difference in the stereoselectivity of the acetals conformers or/and their stereoisomers (Cramer et al. 1997; Plavec et al. 1996). "
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