Stereoselective synthesis of monosaccharides

Mukaiyama T, Suzuki K, Yamada T, Tabusa F (1990) 4-0-Benzyl-23-0-isopro-pylidene-L-threose a useful building block for stereoselective synthesis of monosaccharides. Tetrahedron 46 265... 

Mukaiyama, T, Shiina, I, Kobayashi, S, A convenient and versatile route for the stereoselective synthesis of monosaccharides via key chiral synthons prepared from achiral sources, Chem. Lett, 2201-2204, 1990. 

A general method for the stereoselective synthesis of monosaccharides from furan compounds [30, 31] has provided a possible route to higher-carbon sugars. 

Besides stereoselective synthesis of various monosaccharides, stereoselective reaction for the preparation of glycosides is an important problem in the synthetic field of carbohydrate chemistry. However, the classical methods, which require the assistance of heavy metal salts or drastic reaction conditions, are still employed by and large in the synthesis of such compounds. Taking these disadvantages into consideration, new glycosylation reactions, which proceed under mild reaction conditions with high selectivity, have been developed and exploited. 

Various types of commercially available chiral precursors, generally members of the chiral pool, have been used for the stereoselective synthesis of chiral 5,6-dihydropyran-2-ones [6] (i) carbohydrates, mainly monosaccharides 7, 19, 30] (ii) chiral hydroxy acids [8, 20, 31] (iii) chiral epoxides [9, 21, 32] and (iv) other various types of chitons, including those prepared with the aid of microorganisms or enzymes [10, 22, 33]. As discussed above, there are cases in which one or two of the stereogenic carbons of the chiral precursor are transmitted intact to C-5/C-6 of the pyrone ring of the target molecule. In other cases, however, these carbons are not transferred as such and may even disappear, but only after they have influenced the formation of other stereocenters via internal induction. 

Typical applications of the DHAP aldolases indude the synthesis of monosaccharides and derivatives of sugars from suitable functionalized aldehyde precursors. High conversion rates and yields are usually achieved with 2- or 3-hydroxyaldehydes, because for these compounds reaction equilibria benefit from the cyclization of the products in aqueous solution to give more stable fiiranose or pyranose isomers (Figure 5.32). For example, enantiomers of glyceraldehyde are good substrates, and stereoselective addition of dihydroxyacetone phosphate produces enantiomerically pure ketohexose... 

A typical procedure calls for reaction of the hemiacetal donor with dicydohexyl carbodiimide and copper(I) chloride (0.1 equiv) at 80 °C, followed by an addition of the acceptor and continued heating. As an early demonstration of this protocol, oc-riboside 86 was prepared in moderate yield but with exclusive stereoselectivity [141]. Further measures were required for the glycosylation of monosaccharide acceptors, such as addition of p-toluenesulfonic add (0.1 equiv) to promote the formation of disaccharide 87 [144]. The method was more suitably applied to the synthesis of O-acyl glycopeptides, as evidenced by the formation of 88 in 60% yield [143,144]. Various peptides with non-nudeophilic side chains were found to be amenable to this stereoselective reaction. The [3-selectivity was suggested to arise from a preponderance of the a-isourea intermediate 85 in the activation step. 

C.-H. Lin, T. Sugai, R. L. Halcomb, Y. Ichikawa, and C. H. Wong, Unusual stereoselectivity in sialic acid aldolase-catalyzed aldol condensations Synthesis of both enantiomers of high-carbon monosaccharides, J. Am. Chem. Soc. 774 10138 (1992). 

Synthesis of chiral monosaccharides. Masamune, Sharpless, and coworkers2 have developed a general, iterative sequence for addition of two chiral hydroxymethy-lene units to an aldose. The key step involves regio- and stereoselective ring opening... 

---