Z-and E-phosphonate analogues 12 and 13 derived from cyclopropavir and the corresponding cyclic phosphonates 14 and 15 were synthesized and their antiviral activity was investigated. The 2,2-bis (hydroxymethylmethylenecyclopropane acetate (17) was transformed to tetrahydropyranyl acetate 18. Deacetylation gave intermediate 19 which was converted to bromide 20. Alkylation with diisopropyl methylphosphonate afforded after protecting group exchange (21 to 22) acetylated phosphonate intermediate 22. Addition of bromine gave the dibromo derivative 16 which was used in the alkylation-elimination procedure with 2-amino-6-chloropurine to give Z-and E-isomers 23 and 24. Hydrolytic dechlorination coupled with removal of all protecting groups gave the guanine phosphonates 12 and 13. Cyclization afforded the cyclic phosphonates 14 and 15. Z-Phosphonate 12 was a potent and non-cytotoxic inhibitor of human and murine cytomegalovirus (HCMV and MCMV) with EC 50 2.2-2.7 and 0.13 μM, respectively. It was also an effective agent against EpsteinBarr virus (EBV, EC 50 3.1 μM). The cyclic phosphonate 14 inhibited HCMV (EC 50 2.4-11.5 μM) and MCMV (EC 50 0.4 μM) but it was ineffective against EBV. Both phosphonates 12 and 14 were as active against two HCMV Towne strains with mutations in UL97 as they were against wild-type HCMV thereby circumventing resistance due to such mutations. Z-Phosphonate 12 was a moderate inhibitor of replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) but it was a potent agent against varicella zoster virus (VZV, EC 50 2.9 μM). The cyclic phosphonate 14 lacked significant potency against these viruses. E-isomers 13 and 15 were devoid of antiviral activity.

[structure: see text] The first total synthesis and stereochemical definition of isodomoic acid G has been achieved. The key nickel-catalyzed coupling of an alkynyl enone with an alkenylzirconium allows formation of the pyrrolidine ring and most of the stereochemical features in a single step. This report provides the first total synthesis application of this new reaction and illustrates its utility in the stereoselective preparation of highly substituted 1,3-dienes.

In this paper we report on the synthesis and characterization of three cobalt complexes described as [CoII(L1)2] (1), [CoII(L2)] (2), and [CoIII(L1)2]ClO4 (3). These complexes contain the deprotonated forms of the [NN′O] tridentate ligand HL1 and its newly synthesized [N2N′2O2] hexadentate counterpart H2L2, namely, 2,4-diiodo-6-((pyridine-2-ylmethylamino)methyl)phenol and 6,6′-((ethane-1,2-diylbis((pyridin-2-ylmethyl) azanediyl))bis(methylene))bis(2,4-diiodophenol). Characterizations for 1–3 include electrospray ionization (ESI) spectrometry, infrared, and UV–visible spectroscopies, and elemental analyses. A detailed 1H-NMR study was conducted for 3 and X-ray structural data was obtained for 2. The viability of this series as potential agents for proteasome inhibition and cell apoptotic induction involving PC-3 cancer cells is presented comparing the behavior of the untethered [NN′O]2 six-coordinate 1 and 3 and the tethered counterpart 2 with a 1:1 metal-to-ligand ratio. It is observed that the tethering in 2 decreases inhibition activity. When 1 and 3 are compared, the most inert, but redox-active, cobalt(III) species shows the highest chymotrypsin-like activity inhibition on purified proteasome and PC-3 cancer cells. A hypothesis based on the role of oxidation states for proteasome inhibition is offered.

The synthesis of a series of α-trifluoromethylcyclohexanols and analogous trimethylsilyl ethers by addition of the Ruppert-Prakash reagent to substituted cyclohexanones is presented. A method for the assignment of configuration of such compounds and of related α-trifluoromethylcyclohexylamines and of quaternary trifluoromethyl-substituted carbons is described based on the determination of the 3JCH coupling constant between the fluorine decoupled 13CF3 resonance and the vicinal hydrogens. This method is dubbed Fluorine-Decoupled Carbon Spectroscopy and abbreviated FDCS. The method is also applied to the configurational assignment of substances bearing mono-, di-, and perfluoroalkyl rather than trifluoromethyl groups. The configuration of all substances was verified by either 1H,19F heteronuclear Overhauser spectroscopy (HOESY) or by X-ray crystallography. The relative merits of FDCS and HOESY are compared and contrasted. 2JCH, 3JCH, and 4JCH to 19F decoupled CF3 groups in alkenes and arenes have also been determined and should prove useful in the structural assignment of trifluoromethylated alkenes and arenes.

[reaction: see text]. A procedure for the chemical synthesis of [3-15N]-labeled pseudouridine and a methylated derivative was developed. A suitably protected pseudouridine precursor was nitrated at N3 followed by treatment with 15NH4Cl to afford the 15N-labeled product in six steps with a 20% yield. This methodology will allow for the production of RNAs with [3-15N]pseudouridine and [3-15N-methyl]pseudouridine at specific locations.