BoC-D-Styrylalanine dicyclohexylamine salt

Fumagillin, an antibiotic compound produced by Aspergillus fumigatus, is effective against microsporidia and various Amoeba species, but is also toxic when administered systemically to mammals. Furthermore, a recent in vivo study by Stanimirovic Z et al. 2007: (Mutat Res 628:1-10) indicated genotoxic effects of fumagillin. The aim of the present study was to investigate and explain the clastogenic effects of fumagillin (in the form of fumagillin dicyclohexylamine salt) on human peripheral blood lymphocytes in vitro by sister-chromatid exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN) tests. The mitotic index (MI), proliferation index (PI), and nuclear division index (NDI) were calculated to evaluate the cytotoxic potential of fumagillin. Five concentrations of fumagillin (0.34, 0.68, 1.02, 3.07, and 9.20 microg/ml) were applied to lymphocyte cultures. All the tested concentrations of fumagillin increased the frequency of SCE per cell significantly (P < 0.

Fumagillin is extensively used to control nosema disease in apiculture. In the commercial formulation, fumagillin is present as a salt in an equimolar quantity with dicyclohexylamine (DCH). In this study DCH was observed to be significantly more resistant to degradation in honey than fumagillin using LC-MS/MS analysis. Observed half-lives for DCH ranged from a minimum of 368 days when kept at 34 °C in darkness, to a maximum of 852 days when stored at 21 °C in darkness. A maximum half-life of 246 days was observed for fumagillin in samples kept in darkness at a temperature of 21 °C. The observed half-life of fumagillin was estimated to be 3 days when exposed to light at 21 °C, and complete decomposition was observed after 30 days under the same conditions. The stability of DCH, combined with its genotoxicity and tumorigenic properties make it an important potential contaminant in honey destined for human consumption.

Organic salts based on dicyclohexylamine and substituted/unsubstituted cinnamic acid exhibit efficient gelation of organic fluids, including selective gelation of oil from an oil/water mixture. Among the cinnamate salts, dicyclohexylammonium 4-chlorocinnamate (1), 3-chlorocinnamate (2), 4-bromocinnamate (3), 3-bromocinnamate (4), 4-methylcinnamate (5) and the parent cinnamate (6) are gelators, whereas 2-chlorocinnamate (7), 2-bromocinnamate (8), 3-methylcinnamate (9), 2-methylcinnamate (10) and hydrocinnamate (11) are non-gelators. Non-gelation behaviour of 11 and various benzoate derivatives 12-18 indicate the significance of an unsaturated backbone in the gelation behaviour of the cinnamate salts. A structure-property correlation based on the single-crystal structures of most of the gelators (1, 3, 5 and 6) and non-gelators, such as 7, 8, 10-18, indicates that the prerequisite for the one-dimensional (1D) growth of the gel fibrils is mainly governed by the 1D hydrogen-bonded network involving the ion pair.

A practical, chromatography-free synthesis of potent cathepsin K inhibitor 1 is described. The addition of 4-bromophenyllithium to an alpha-trifluoromethylimine derived from commercially available (S)-leucinol was accomplished in a highly diastereoselective manner (97.6% de, 91% yield). Subsequent Suzuki cross-coupling afforded biaryl 7. Oxidation of the alcohol and sulfide functionalities led to the formation of carboxylic acid 8. Crystallization of 7 and acid 8 as its dicyclohexylamine salt gave excellent impurity rejection. The final amide coupling with commercially available aminoacetonitrile hydrochloride afforded 1 in excellent purity (99.6A% by HPLC, 100% de, <3 ppm Pd, W, Cr).