Current Organic Chemistry - Volume 6, Issue 4, 2002

Oxazolidinethiones and thiazolidinethiones constitute a class of versatile chiral auxiliaries for asymmetric synthesis. Their easy preparation from readily available β-amino-alcohols and the high levels of asymmetric induction they provide make them excellent chiral auxiliaries useful for the preparation of chiral intermediates in the synthesis of natural products. These chiral auxiliaries have been utilized in a wide variety of synthetic transformations such as asymmetric aldol condensation, stereoselective alkylation of different electrophiles, stereoselective differentiation of enantiotopic groups in molecules bearing prochiral centers, and other interesting applications. This review attempts to summarize the preparation, synthetic applications, and cleavage of oxazolidinethiones and thiazolidinethiones, as well as the manipulation of chiral intermediates obtained in asymmetric transformations involving these chiral auxiliaries.

Michael addition reactions between nucleophilic glycine equivalents and α,β-unsaturated carboxylic acid derivatives, represent the most methodologically concise and generalized approach to the family of χ-constrained five-carbon-atom amino acids. Such amino acids are of critical importance in the de novo peptide design and for elucidation of peptide / protein three-dimensional structure and its biological function / activity. This review summarizes all of the synthetically and methodologically important achievements in the field published to date. The review consists of two major parts summarizing the literature methods and the author's own results on the development of highly diastereoselective, organic base-catalyzed room temperature Michael addition reactions. Discussion on each particular method includes highlighting of the synthetic opportunities and limitations, practicality and efficiency of the procedures and mechanistic

Phytosphingosines constitute a group of functionally related, long-chain aliphatic 2-amino-1,3,4-triols of which D-ribo-C18-phytosphingosine ((2S,3S,4R)-2-aminooctadecane-1,3,4-triol) is the most prevalent. D-ribo-Phytosphingosine is a bioactive lipid and is reported to be a potential heat stress signal in yeast cells. Phytosphingosines are widely distributed as structural components of sphingolipids in yeast, fungi, mammalian tissues and marine organisms. The long-chain base (phytosphingosine component) of the majority of the phytosphingolipids has 18-carbons minor amounts of other chain lengths, especially C20, are also found, depending on their origin. Some of these phytosphingolipids exhibit important physiological activities. For example, there are α-and β-galactosyl- and glucosylphytoceramides that possess high tumor inhibitory potency. Due to the variety and significance of their biological activities and their scarcity in nature, phytosphingosines have become important synthetic targets. In general, approaches can be placed into three main categories. The first two rely on the chiral pool of amino acids and carbohydrates as the foundation for the asymmetric centers. Most amino acid strategies utilize (L)-serine. The carbohydrate-based approaches are the most abundant and employ a variety of common sugars and amino sugars. The third category of syntheses is based on asymmetric transformations. In this review the biological importance of phytosphingosines will be highlighted and approaches to their synthesis will be reviewed.

The reverse micellar medium consists of tiny water droplets stabilized by surfactants in a bulk water-immiscible, organic solvent. The solutions are optically transparent and almost any enzyme can be solubilized in reverse micelles without loss of its specific activity. Reverse micelles provide a unique microenvironment for enzymes to react with water insoluble or poorly soluble compounds present in the organic phase. It is possible to use even multi-enzyme systems to carry out a sequence of transformations. The presence of surfactant in the medium helps to overcome diffusion resistance and enzymes entrapped in hydrophilic gels such as polyacrylamide or calcium alginate can also be used for biotransformation of hydrophobic substrates and recycled several times. The solubilization of gelatin in reverse micelles to form organogels and solubilization of microbial cells in water-in-oil microemulsions without loss of viability have opened up new possibilities. Entrapped enzymes in such organogels or ’gelozymes‘ can be used in organic solvents without the use of surfactant, simplifying the workup procedure. Enzymatic reactions requiring co-factors such as reduction with alcohol dehydrogenase and epoxidation with monooxygenase can be carried out with whole cells. This review discusses various applications of enzymes entrapped in reverse micelles and organogels for resolution of amino acids, peptide synthesis, reduction of prochiral ketones, synthesis of glycerides and chiral intermediates useful in production of agrochemicals and pharmaceuticals. The possibilities of substrate isolation, surfactant reuse and enzyme recycling with the help of bioreactors are also discussed.