ABSTRACT
We report a new anionic cascade for assembling 2,4-substituted benzoate esters in one pot from racemic ß-fluoro-substituted conjugated tert-butylsulfinyl imines and 3-substituted methyl 2-butenoates. Dienolate formation triggers a Mannich addition followed by an amino-Cope like rearrangement, which results in immediate elimination of fluoride by a lithiated enamine. The newly formed 1,4-diene intermediate contains a highly acidic proton which is spontaneously deprotonated, leading to a facile intramolecular cyclization followed by sulfinamide group elimination and aromatization.
Subject(s)
Benzoates , Esters , Stereoisomerism , Cyclization , Imines , AnionsABSTRACT
The FDA Green Book is a list of all drug products that have been approved by the FDA for use in veterinary medicine. The Green Book, as published, lacks structural information corresponding to approved drugs. To address this gap, we have compiled the structural data for all FDA Green Book drugs approved through the end of 2019. Herein we discuss the relevance of this data set to human drugs in the context of structural classes and physicochemical properties. Analysis reveals that physicochemical properties are highly optimized and consistent with a high probability of favorable drug metabolism and pharmacokinetic properties, including good oral bioavailability for most compounds. We provide a detailed analysis of this data set organized on the basis of structure and function. Slightly over half (51%) of vet drugs are also approved in human medicine. Combination drugs are biologics are also discussed.