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Sterically hindered N-alkoxy amines 3 are synthesized in good yields by coupling nitroxides 2 with hydrocarbyl radicals generated in situ by t-BuOOH hydrogen abstraction from hydrocarbons. The reaction is catalyzed by copper halides as well as by onium iodides.

The simplified sialyl Lewisx mimic 5 containing a D-arabinose, a 3-cyclohexyl-2-hydroxypropanoate, and a tetrahydropyran building block instead of L-fucose, sialic acid, and N-acetylglucosamine, respectively was synthesized. Compound 5 was 10-fold more potent than sLex in a static E-selectin binding assay and showed at 50 μM 75% inhibition in a dynamic-flow assay in which sLex did not inhibit neutrophil rolling at up to 1000 μM. Compound 7 with a lactic acid instead of sialic acid building block showed threefold improved potency compared to sLex.

A protocol for the functionalization of polyaspartimide ( PAI ) with carbohydrates containing an amino funtion at the reducing end to give biodegradable neoglycoconjugates such as 4 is presented. Scope and limitation of the strategy with respect to the preparation of multivalent sialyl Lewis x 5 are discussed.

The relation of the solution and bioactive conformation of sialyl Lewis x (sLe(x)) has been addressed by chemical means. To mimic the preferred solution conformation of sLe(x) 1, the more rigid analog 2 has been designed and synthesized. The sialic acid residue of 1 was replaced by a carboxylic acid function which is fixed in the equatorial position of a six membered ring acetal fused to galactose. Due to entropic considerations, an increased biological activity could be expected if the preferred solution conformation and bound form of sLe(x) were similar. Since mimic 2 was found to be inactive in an E-selectin binding assay, the bound form of sLe(x) most probably differs from the prevailing solution conformation.

The first highly enantioselective, catalytic asymmetric synthesis of di-des-methylsibutramine 3 is described. Dienamide 10, prepared by acetic acid anhydride quenching of the condensation product of nitrile 4 with a methallyl magnesium chloride, proved to be an excellent substrate for ruthenium-catalyzed asymmetric hydrogenation with atropisomeric diphosphine ligands. Hydrogenation with a ruthenium/(R)- MeOBiPheP catalyst at S/C = 500, gave the chiral amide (R)-9 in 98.5% ee in almost quantitative yield. After acidic amide hydrolysis the desired amine (R)-3 was obtained without erosion of enantioselectivity. It is anticipated that the overall process will be amenable to large-scale production.

The relation of the solution and bioactive conformation of sialyl Lewis x (sLex) has been addressed by chemical means. To mimic the preferred solution conformation of sLex 1, the more rigid analog ...

The preparation, analysis, and reactions of novel, highly stereoselective cyclopentadienyldialkoxyallyltitanium reagents, available in both enantiomeric forms, are described. Chiral monochlorotitanates are readily prepared from CpTiCl 3 or Cp.TiCl 3 and chiral 1,4-diols, which in turn are obtained from tartrate ester acetals by Grignard addition. The resulting stable seven-membered titanacycles have been analyzed by 1 H, 13 C, and 49 Ti NMR spectroscopy. The structures of two representatives, the complexes 15 and 20, are confirmed by X-ray diffraction