Application of the palladium-catalyzed borylation/Suzuki coupling (BSC) reaction to the synthesis of biologically active biaryl lactams.
The palladium-catalyzed, two-step, one-pot borylation/Suzuki coupling (BSC) reaction was developed to synthesize sterically hindered 2,2'-disubstituted biphenyl and phenyl-indole compounds in a short, simple, and efficient manner from two easily accessible aryl halides. High yields can be obtained by choosing properly both components according to their rough electronic properties. The illustration of the utility of this method was provided by the solution and solid-phase synthesis of seven- or eight-membered biphenyl lactams 5a-e, as well as paullone 3a. These compounds exhibit moderate albeit significant cytotoxicities and may serve as structural models for future medicinal chemistry developments.
Baudoin
Olivier
O
Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France. baudoin@icsn.cnrs-gif.fr
Cesario
Michèle
M
Guénard
Daniel
D
Guéritte
Françoise
F
D000470:Alkaloids / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001896:Boron Compounds / Q000737:chemistry; D002384:Catalysis; D003078:Colchicine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007212:Indolizines; D020128:Inhibitory Concentration 50; D007624:KB Cells / Q000187:drug effects; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000470:Alkaloids; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D001896:Boron Compounds; D004791:Enzyme Inhibitors; D007212:Indolizines; D007769:Lactams; C009170:rhazinilam; D010165:Palladium; C032782:allocolchicine; D018844:Cyclin-Dependent Kinases; D003078:Colchicine