title: A general strategy for the synthesis of cyclic N-aryl hydroxamic acids via partial nitro group reduction.
abstract: We describe a generalized approach to stereocontrolled synthesis of substituted cyclic hydroxamic acids (3-amino-1-hydroxy-3,4-dihydroquinolinones) by selective reduction of substituted 2-nitrophenylalanine substrates. Compounds in this series have antibacterial properties and have also recently been reported as KAT II inhibitors. The key nitrophenyl alanine intermediates are prepared enantioselectively in excellent yield by phase transfer catalyzed alkylation of the corresponding nitrobenzyl bromides. The scope and limitations of the reductive cyclization transformation have been explored with attention to the effects of substitution pattern and electronics on reaction efficiency and byproduct formation. In addition, a novel activated trifluoroethyl ester cyclization strategy has been developed as an alternate approach to the most sterically demanding systems in this series.
authors: Neuroscience Chemistry, Pfizer Worldwide R&D, Eastern Point Rd., Groton, Connecticut 06340, USA. laura.mcallister@pfizer.com
authors: Laura A
authors: LA
authors: McAllister
authors: Bruce M
authors: BM
authors: Bechle
authors: Amy B
authors: AB
authors: Dounay
authors: Edelweiss
authors: E
authors: Evrard
authors: Xinmin
authors: X
authors: Gan
authors: Somraj
authors: S
authors: Ghosh
authors: Ji-Young
authors: JY
authors: Kim
authors: Vinod D
authors: VD
authors: Parikh
authors: Jamison B
authors: JB
authors: Tuttle
authors: Patrick R
authors: PR
authors: Verhoest
mesh_terms: D003500:Cyclization; D004952:Esters; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D009574:Nitro Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D019346:Sodium Acetate / Q000737:chemistry; D013379:Substrate Specificity; D017971:Tin Compounds / Q000737:chemistry
chemical_list: C540473:2-nitrophenylalanine; D004952:Esters; D006877:Hydroxamic Acids; D009574:Nitro Compounds; D017971:Tin Compounds; C023599:stannous chloride; D019346:Sodium Acetate; D010649:Phenylalanine