Dearomatizing anionic cyclization of phosphonamides. A route to phosphonic acid derivatives with antitumor properties.
Deprotonation of bis(N-benzyl-N-methyl)-P-arylphosphonic diamides with s-BuLi in THF at -90 degrees C takes place selectively at the benzylic position. The anions undergo intramolecular attack to the P-aryl ring leading to dearomatized species that were trapped with a series of electrophiles (MeOH, ArOH, BnBr, aliphatic and aromatic aldehydes, and benzophenone) in very high yield, and with high regio- and stereocontrol. The dearomatized products were smoothly transformed into gamma-aminophosphonic acids under acidic conditions. Preliminary screening for antitumor activity showed promising levels of activity.
Ruiz-Gómez
Gloria
G
Area de Química Orgánica, Universidad de Almería, Carretera de Sacramento, 04120 Almería, Spain.
Francesch
Andrés
A
Iglesias
María José
MJ
López-Ortiz
Fernando
F
Cuevas
Carmen
C
Serrano-Ruiz
Manuel
M
D000577:Amides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D006801:Humans; D008094:Lithium / Q000737:chemistry; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000577:Amides; D000970:Antineoplastic Agents; D063065:Organophosphonates; D008094:Lithium