Glutarimide Antibiotics. VII. The Synthesis of dl-Neocycloheximide and the Determination of the Cyclohexanone Ring Stereochemistry of Cycloheximide, Its Isomers, and Inactone

The Nielsen condensation of dl-cis-2,4-dimethylcyclohexanone with 3-glutarimidylacetaldehyde has been examined as a synthetic approach to compounds having the gross structure of cycloheximide (I). The sole crystalline product from the reaction is a new isomer of I and has been named dl-neocycloheximide. A combination of chemical methods and n.m.r. spectroscopy has been used to elucidate completely the cyclohexanone ring stereochemistry of cycloheximide and its stereochemical isomers naramycin-B, isocycloheximide, and neocycloheximide. The skeletal structure of inactone has been confirmed and its stereochemistry has been elucidated. Comments on the stereochemistry of E-73 and streptovitacin-A are noted.