Current Organic Chemistry - Volume 8, Issue 6, 2004

The inexpensive and commercially available chlorosulfonyl isocyanate reacts readily with the variety of nucleophilic olefins to provide unstable [2+2]cycloadducts. The reaction proceeds via concerted mechanism rather than a stepwise process. The electron-donating substituent in the olefin component controls the regiochemistry of the reaction. The cycloaddition is stereospecific, leading from (Z)-olefin to the cis-adduct and from (E)-olefin to the trans-adduct. Increase of the reaction time or the presence of an acid contamination may result either in the epimerization at C(4) of the azetidin-2-one ring or in the rearrangement leading to the opening of the fourmembered ring. The N-deprotection of the [2+2]cycloadducts by reduction of the chlorosulfonyl group results in the formation of stable azetidin-2-ones, useful synthons in the synthesis of β-lactam antibiotics. The discussed reactions are sterically controlled and in many cases take place with a high asymmetric induction. Due to the observed exothermic nature of the cycloaddition, the conformation of the olefin in the transition state resembles, with a high probability, the low-energy ground-state conformation.

The D- and L-form 1,6-anhydrohexopyranoses are valuable building blocks in the synthesis of carbohydrate molecules as well as nature products. Their bicyclo[3.2.1]octane framework possesses rigid conformation that has several advantages and offers unique reactivity patterns in comparison with their corresponding hexopyranoses. A variety of practical and convenient routes developed for their preparation over past two decades have been reviewed and analyzed here. The novel reactions for regioselective discriminations of three hydroxy groups at C2, C3, and C4 via chemical or enzymatic processes, newer methodologies for opening the 1,6-anhydro ring, and their applications to synthesize the biologically significant and structurally diverse oligosaccharides and nature compounds are described.

Microwave irradiation is becoming an increasingly popular method of heating which replaces the classical one because it proves to be a clean, cheap, and convenient method. Often, it affords higher yields and results in shorter reaction times. This method of heating has been extended to almost all areas of chemistry with the exception of the carbohydrate chemistry which has suffered a certain delay, as it is testified by the limited number of applications. The aim of this review is to explore the variety of these applications in carbohydrate chemistry, even if in a limited number, which have been carried out with microwave irradiation as activating agent. Mainly, these concern the selective or unselective protection and deprotection of hydroxyl functionalities, and triglyceride alcoholysis and glycerolysis reactions of industrial interest since these lead to materials for the production of straining, emulsifying and softening agents and moreover for the production of an ecologic fuel (biodiesel). Other aspects of the carbohydrate chemistry such as the syntheses of monosaccharides containing heterocyclic nuclei, or unsaturations, or halogens are also included. Synthetically, the effect on the mutarotation phenomenon, polysaccharides, methanolysis and hydrolysis of saccharides, flavour formation deriving from the interactions of sugars with amino acids, and sterospecific activation of the C-H bond for the deuterium and tritium labelling are reported. In several cases, a comparison is made between results obtained with conventional and microwave-assisted methods.

This article will review the techniques used for the characterization of the N-linked oligosaccharides of glycoproteins to be used in enzyme replacement therapy (ERT), describe the specific role some of these oligosaccharides play in the delivery of these enzymes and outline the syntheses of some relevant fluorogenic and chromogenic carbohydrates that are not commercially available. Without being extensive, this review is meant to provide adequate and relevant background literature and hopes to stimulate organic chemists to find creative solutions for problems associated with glycoproteins, and those faced by biochemists, bioanalytical and protein purification scientists.