Biological Evaluations, NMR Analyses, Molecular Modeling Studies, and Overview of the Synthesis of the Marine Natural Product (-)-Mucosin.

Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (-)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (-)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (-)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (-)-mucosin (1) is also presented.

The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid.

Monohydroxylated polyunsaturated fatty acids belonging to the oxylipin class of natural products are present in marine and terrestrial sources as well as in the human body. Due to their biological activities and role in diverse biosynthetic pathways, oxylipins biosynthesized from eicosapentaenoic acid and arachidonic acid have attracted great interest from the scientific community. One example is 3-hydroxyeicosapentaenoic acid where the absolute configuration at C-3 has only been tentatively assigned. In this paper, studies on acetate type aldol reactions that enabled the preparation of 3-(R)-hydroxyeicosapentaenoic acid (3R-HETE, 2) and its enantiomer are presented.

Atmospheric Chemistry of Methyl Isocyanide-An Experimental and Theoretical Study.

The reaction of CH3NC with OH radicals was studied in smog chamber experiments employing PTR-ToF-MS and long-path FTIR detection. The rate coefficient was determined to be kCH3NC+OH = (7.9 ± 0.6) × 10-11 cm3 molecule-1 s-1 at 298 ± 3 K and 1013 ± 10 hPa; methyl isocyanate was the sole observed product of the reaction. The experimental results are supported by CCSD(T*)-F12a/aug-cc-pVTZ//M06-2X/aug-cc-pVTZ quantum chemistry calculations showing the reaction to proceed primarily via electrophilic addition to the isocyanide carbon atom. On the basis of the quantum chemical data, the kinetics of the OH reaction was simulated using a master equation model revealing the rate coefficient to be nearly independent of pressure at tropospheric conditions and having a negative temperature dependence with kOH = 4.2 × 10-11 cm3 molecule-1 s-1 at 298 K. Additional quantum chemistry calculations on the CH3NC reactions with O3 and NO3 show that these reactions are of little importance under atmospheric conditions. The atmospheric fate of methyl isocyanide is discussed.

Two-Phase Dibromocyclopropanation of Unsaturated Alcohols Using Flow Chemistry.

Dibromocyclopropanations are conventionally done by addition of dibromocarbene to alkenes under phase-transfer conditions in batch reactions using a strong base (50% NaOH (aq)), vigorous stirring and long reaction times. We have shown that cyclopropanation of unsaturated alcohols can be done under ambient conditions using continuous flow chemistry with 40% (w/w) NaOH (aq) as the base. The reactions were generally rapid; the yields were comparable to yields reported in the literature for the conventional batch reaction.

The binding of pentapeptides to biological and synthetic high affinity heparin.

Pentapeptides have been shown to bind the synthetic heparin fondaparinux (Arixtra) as well the biological heparins dalteparin (Fragmin) and salmon heparin. In contrast to heparin binding consensus sequences, the pentapeptides are acidic or neutral, with no arginine or histidine residue. The peptides showed an effect on in vitro heparin anti-factor X activity with a reduction of fondaparinux activity by 65-95%. Heparin binding was further studied by using peptide solid phase chromatography and NMR analysis.