ABSTRACT
Polyene cyclization of compounds 3 and 4 under catalysis with AlCl3 and/or SnCl4 gave rise to complex bicyclic products 8 and 9, structures of which were highly unexpected, and X-ray analyses were invoked for unambiguously structural identification. Mechanistically, a tandem sigma-bond rearrangement process, including an unusual through-space 1,5-hydride or 1,3-alkyl shift as a key operation, is proposed.
Subject(s)
Alkenes/chemistry , Ketones/chemistry , Catalysis , Cinnamates/chemistry , Cyclization , Molecular Structure , Stereoisomerism , Zinc/chemistryABSTRACT
An operationally simple and high-yielding procedure has been developed for the conversion of primary amides to the corresponding nitriles, using ethyl dichlorophosphate/DBU as the mild dehydrating agent.
Subject(s)
Amides/chemistry , Nitriles/chemistry , Molecular Structure , Water/chemistryABSTRACT
A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, Ki = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 microM) for SARS CoV and 5.2 log (at 1.25 microM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 A) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.
Subject(s)
Antiviral Agents/chemical synthesis , Carbamates/chemical synthesis , Cysteine Endopeptidases/chemistry , Dipeptides/chemical synthesis , Viral Proteins/antagonists & inhibitors , Viral Proteins/chemistry , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Carbamates/chemistry , Carbamates/pharmacology , Cell Line , Chlorocebus aethiops , Coronavirus 229E, Human/drug effects , Coronavirus 3C Proteases , Crystallography, X-Ray , Dipeptides/chemistry , Dipeptides/pharmacology , Drug Stability , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Mice , Models, Molecular , Molecular Structure , Rats , Severe acute respiratory syndrome-related coronavirus/drug effects , Structure-Activity Relationship , Virus Replication/drug effectsABSTRACT
Enone phosphonates 1 and 2 were found to be excellent dienophiles for the Diels-Alder reaction, giving phosphonate-containing polycycles, and the phosphonate group of the resulting adducts facilitated both the installation of an angular alkyl group via a reductive alkylation process and the regioselective generation of a ring junction double bond via an intramolecular Wadsworth-Horner-Emmons reaction.