Recent Synthetic Approaches Toward Non-anomeric Spiroketals in Natural Products
| Autor: | Sylvain Favre, Pierre Vogel, Sandrine Gerber-Lemaire |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Anomer
Anomeric effect Stereochemistry gauche effect Pharmaceutical Science Review Heterolysis Analytical Chemistry lcsh:QD241-441 Structure-Activity Relationship chemistry.chemical_compound Drug Stability lcsh:Organic chemistry Drug Discovery Structure–activity relationship Spiro Compounds Physical and Theoretical Chemistry Furans Conformational isomerism spirocyclization anomeric effect Biological Products Organic Chemistry Acetal non-anomeric interaction anomeric interaction Oxygen atom chemistry thermodynamic equilibration Chemistry (miscellaneous) Molecular Medicine Stereoselectivity kinetic control Spiroketal |
| Zdroj: | Molecules, Vol 13, Iss 10, Pp 2570-2600 (2008) Molecules |
| ISSN: | 1420-3049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|