ABSTRACT
Viruses belonging to the Flaviviridae family cause clinically significant diseases in humans and animals. This family includes three genera: Pestivirus [including bovine viral diarrhea virus (BVDV)], Flavivirus [including yellow fever virus (YFV), dengue virus, and West Nile virus (WNV)], and Hepacivirus [including hepatitis C virus (HCV)]. BVDV is responsible for major losses in cattle, causing a range of clinical manifestations, and is also a problematic contaminant in the laboratory. Noncytopathic BVDV infection can remain unnoticed and infect laboratory cell lines through its presence in contaminated bovine serum used in cell culture. BVDV is considered to be a valuable surrogate virus model for identifying and characterizing antiviral agents to be used against HCV. In some aspects of viral replication, BVDV is more advantageous than the currently used HCV replicon systems. In this review, we report the design, synthesis, and activity against BVDV of a series of compounds assayed until now.
Subject(s)
Antiviral Agents/pharmacology , Diarrhea Viruses, Bovine Viral/drug effects , Drug Design , Animals , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Bovine Virus Diarrhea-Mucosal Disease/drug therapy , Bovine Virus Diarrhea-Mucosal Disease/virology , Cattle , Nucleosides/chemical synthesis , Nucleosides/chemistry , Nucleosides/pharmacologyABSTRACT
Several polyfunctionalized cyclobutane derivatives have been synthesized using commercial (-)-alpha-pinene and (-)-verbenone as chiral precursors. Thus, oxidative cleavage of these compounds by using ruthenium trichloride afforded quantitatively (-)-cis-pinonic and (-)-cis-pinononic acids, respectively, without epimerization. These products were converted into several types of aldehydes, which are the key intermediates in the synthesis of cyclobutane dehydro amino acids via Wittig-Horner condensations with suitable phosphonates. These reactions are highly stereoselective, affording exclusively (Z) isomers, stereochemistry being assessed by NMR experiments. The obtained dehydro amino acids are polyfunctionalized molecules useful for the synthesis of other alpha-amino acids, with additional chiral centers, whose configuration must be induced by the chirality of the terpene employed as a precursor.
