Chemical Synthesis

Observations of nonequilibrium phenomena on the Saturn satellite Titan indicate the occurrence of organic chemical evolution. Features taken from various models of Titan's atmosphere are combined in a working composite model that provides environmental constraints within which different pathways for organic chemical synthesis are assessed. Experimental results and theoretical modeling studies suggest that the organic chemistry of the satellite is dominated by two atmospheric processes: photochemistry and energetic particle bombardment. Photochemical reactions of CH4 in the upper atmosphere can account for the presence of C2 hydrocarbons. Reactions initiated in various levels of the atmosphere by cosmic ray, Saturn ‘wind,’ and solar wind particle bombardment of a CH4‐N2 atmospheric mixture can account for the ultraviolet‐visible absorbing stratospheric haze, the reddish appearance of the satellite, and some of the C2 hydrocarbons. In the lower atmosphere, photochemical processes ...

The epoxidation process of semi-synthetic triterpenoids 2-methyl-3-oxo-19β,28-epoxy- 18α-olean-1-ene, and its allylic alcohol derivatives were examined. 1,2α-epoxide, as the main product, was found to be formed from the starting enone exposed to m-chloroperbenzoic acid (mCPBA). In the case of hydroxy-directed mCPBA-oxidation of triterpenic allyl alcohols and their 3α-alkyl-substituted derivatives, inversion of C1 and C2 asymmetric centers with the formation of 1,2β-epoxyalcohols took place. The synthesis of 2,3α-epoxides was fulfilled from 2,3-dialkyl-substituted C(3) allyl alcohols by the action of pyridinium chlorochromate under [1,3]-oxidative rearrangement conditions. The transformations brought about enabled chiral oleanane derivatives with an oxygen-containing substituent at the C1, C2, and C3 atoms to be obtained. The study also provides information on in silico PASS prediction of pharmacological effects and in vitro evaluation of the cytotoxic activity of the synthesized com...

Stromal cell-derived factor-1α (SDF-1α ) is a member of the chemokine superfamily and functions as a growth factor and chemoattractant through activation of CXCR4/LESTR/Fusin, a G protein-coupled receptor. This receptor also functions as a coreceptor for T-tropic syncytium-inducing strains of HIV-1. SDF-1α antagonizes infectivity of these strains by competing with gp120 for binding to the receptor. The crystal structure of a variant SDF-1α ([N33A]SDF-1α ) prepared by total chemical synthesis has been refined to 2.2-Å resolution. Although SDF-1α adopts a typical chemokine β-β-β-α topology, the packing of the α-helix against the β-sheet is strikingly different. Comparison of SDF-1α with other chemokine structures confirms the hypothesis that SDF-1α may be either an ancestral protein from which all other chemokines evolved or the chemokine that is the least divergent from a primordial chemokine. The structure of SDF-1α reveals a positively charged surface ideal for binding to the negat...

The determination of high resolution three‐dimensional structures by X‐ray crystallography or nuclear magnetic resonance (NMR) is a time‐consuming process. Here we describe an approach to circumvent the cloning and expression of a recombinant protein as well as screening for heavy atom derivatives. The selenomethionine‐modified chemokine macrophage inflammatory protein‐II (MIP‐II) from human herpesvirus‐8 has been produced by total chemical synthesis, crystallized, and characterized by NMR. The protein has a secondary structure typical of other chemokines and forms a monomer in solution. These results indicate that total chemical synthesis can be used to accelerate the determination of three‐dimensional structures of new proteins identified in genome programs.