Current Organic Chemistry - Volume 7, Issue 14, 2003

Applications of the retro Diels-Alder reaction (cycloreversion) under mild conditions for the laboratory preparation of heteromonocycles or condensed-ring heterocycles are reviewed. A new method utilizes diendo- or diexo-3-aminonorbornene-2-carboxylic acids and their derivatives for the formation of heterocyclic ring systems which are difficult to access by other routes or which can be prepared only in complicated multi-step procedures. The synthesis of substituted 1,3-dienes (e.g. furan derivatives) and O,N- or N,N-heterocycles (oxazoles, isoxazoles, pyrazoles, imidazoles, triazoles, pyrimidinones, oxazinones, pyridazinones etc) are discussed.

In this account we will present and critically analyze the different synthetic strategies that have been reported in the literature for the synthesis of kinamycin C, one the rare naturally occurring diazo compounds, with interesting biological activities.

The Paterno-Buchi reaction on furan derivatives is reviewed. The photochemical reaction of furan derivatives in the reaction with carbonyl compounds gives the corresponding monoadduct with high regio- and stereoselectivity. When the reaction is carried out in benzene, a large amount of the diadduct can be obtained. The exo stereoselectivity at C-6 was explained assuming the presence of a secondary orbital effect on spin orbit coupling. Regio- and stereoselectivity of the reaction of carbonyl compounds with 2,3-dihydrofuran is described. Applications of the reaction to the synthesis of 2- and 3-furylmethanol derivatives is reported. The synthesis of asteltoxin, avenaciolide, and oxetanocin is also reported. Asymmetric reactions on chiral glyoxylate is reported. The low diastereoselectivity of the reaction with chiral ketones and aldehydes is discussed. Finally, the high diastereoselectivity observed in the reaction with 2-furylmethanol derivatives is reported.

In recent years a number of compounds containing bis-spiroacetal systems have been isolated from nature. Predominantly of dinoflagellate origin, they have stimulated much synthetic interest due to their potent biological activity and synthetically challenging structural features. Although the chemistry of bicyclic spiroacetals is well understood, that of the tricyclic bis-spiroacetals has been less fully explored. This review describes the strategies employed to construct bis-spiroacetals with particular reference to stereochemical issues associated with the quaternary spirocentres.

The development of novel building blocks which are capable to self-assemble and the design of artificial receptors for a given substrate are two main goals in supramolecular chemistry. Herein, we describe the synthesis and evaluation of a de novo designed new binding motif for carboxylates in polar solution, the guanidiniocarbonyl pyrroles. The thermodynamic properties of this new receptor class were intensively studied both experimentally by NMR, X-ray and ESI MS, and theoretically using molecular modelling. These studies led to a detailled structural and thermodynamic understanding of the recognition event. Futhermore, a comparative thermodynamic study allowed us to arrive at a supramolecular structure-binding relationship (SSBR) for the complexation of carboxylates by this receptor class. Based on this novel recognition motif, new supramolecular structures can be designed. Self-complementary guanidiniocarbonyl pyrrole / carboxylate zwitterions form intramolecular loops, dimers or supramolecular oligomers depending on the molecular structure of the zwitterion and the experimental conditions. Guanidiniocarbonyl pyrrole cations can also be used as receptors for the side chain selective- and stereoselective complexation of amino acids in aqueous solvents. By incorporating such guanidiniocarbonyl pyrrole units into a combinatorial receptor library, one can also identify receptors for the effective complexation of biologically relevant oligopetides.