ABSTRACT
We report the diastereoselective and chromatography-free syntheses of four 2-phenyl-6-alkyl-3-aminopiperidines. Ring construction was accomplished through a nitro-Mannich reaction linking a nitroketone and phenylmethanimine, followed by a ring-closure condensation. Relative stereocontrol was achieved between C-2 and C-3 by kinetic protonation of a nitronate or by equilibration of the nitro group under thermodynamic control. Stereocontrol at C-6 was accomplished by utilizing a variety of imine reduction methods. The C-2/C-6-cis stereochemistry was established via triacetoxyborohydride iminium ion reduction, whereas the trans relationship was set either by triethylsilane/TFA acyliminium ion reduction or by Lewis acid catalyzed imine reduction with lithium aluminum hydride.
Subject(s)
Ketones/chemistry , Nitro Compounds/chemistry , Piperidines/chemical synthesis , Benzene Derivatives/chemical synthesis , Kinetics , StereoisomerismABSTRACT
Aryl and hetero aryl substituted 3,6-ketals of 15-membered azalide analogues were synthesized and were found to have potent in vitro antibacterial activity against veterinary pathogens, including Staphylococcus aureus and Pasteurella multocida.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Gonadotropin-Releasing Hormone/analogs & derivatives , Gonadotropin-Releasing Hormone/pharmacology , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/pharmacology , Animals , Cattle , Cattle Diseases/microbiology , Female , Gonadotropin-Releasing Hormone/chemical synthesis , Mastitis, Bovine/microbiology , Mice , Microbial Sensitivity Tests , Pasteurella multocida/drug effects , Pasteurellosis, Pneumonic/microbiology , Staphylococcus aureus/drug effects , Structure-Activity RelationshipABSTRACT
3,6-Ketals of 15-membered azalide pseudoaglycones are a novel series of macrolide antibiotics. The aromatic derivatives of the azalide 3,6-ketals demonstrated potent antibacterial activities against both Gram-positive and Gram-negative bacteria.