Functional group directed C-H borylation.

The direct borylation of hydrocarbons via C-H activation has reached an impressive level of sophistication and efficiency, emerging as a fundamental tool in synthesis because of the versatility offered by organoboron compounds. As a remarkable particularity, the catalytic systems originally developed for these reactions are relatively insensitive to directing effects, and the regioselectivity of the borylations is typically governed by steric factors. Likely stimulated by the great synthetic potential of the expected functionalised organoboranes, however, many groups have recently focused on the development of complementary strategies for directed, site-selective borylation reactions where a directing group controls the course of the reaction. In this tutorial review, the different strategies and findings related to the development of these directed borylation reactions via C(sp(2))-H or C(sp(3))-H activation will be summarized and discussed.

Stereoselective nucleophilic formylation and cyanation of alpha-alkoxy- and alpha-aminoaldehydes.

The spontaneous 1,2-addition of formaldehyde N,N-dialkylhydrazones to carbohydrate-derived alpha-alkoxyaldehydes takes place under neutral conditions and in the absence of catalysts or promoters to afford the corresponding alpha-hydroxyhydrazones in good to excellent yields and with highly anti diastereoselectivities. Subsequent transformations of the hydrazono group into aldehydes and nitriles following known procedures provide a new entry into the homologation of carbohydrates and the synthesis of cyanohydrins, respectively. Additionally, reaction of methyleneaminopyrrolidine with N-Boc-protected alpha-aminoaldehydes from natural amino acids efficiently affords the corresponding adducts under the same conditions. From these adducts, a variety of biologically interesting alpha-hydroxy-beta-aminocarbonyl compounds can be accessed upon manipulation of the hydrazone moiety.

The activation of fibroblast growth factors by heparin: synthesis, structure, and biological activity of heparin-like oligosaccharides.

An effective strategy has been designed for the synthesis of oligosaccharides of different sizes structurally related to the regular region of heparin; this is illustrated by the preparation of hexasaccharide 1 and octasaccharide 2. This synthetic strategy provides the oligosaccharide sequence containing a D-glucosamine unit at the nonreducing end that is not available either by enzymatic or chemical degradation of heparin. It may permit, after slight modifications, the preparation of oligosaccharide fragments with different charge distribution as well. NMR spectroscopy and molecular dynamics simulations have shown that the overall structure of 1 in solution is a stable right-hand helix with four residues per turn. Hexasaccharide 1 and, most likely, octasaccharide 2 are, therefore, chemically well-defined structural models of naturally occurring heparin-like oligosaccharides for use in binding and biological activity studies. Both compounds 1 and 2 induce the mitogenic activity of acid fibroblast growth factor (FGF1), with the half-maximum activating concentration of 2 being equivalent to that of heparin. Sedimentation equilibrium analysis with compound 2 suggests that heparin-induced FGF1 dimerization is not an absolute requirement for biological activity.