[Isomeric phenanthridines from 1,2-dihydro-5-methyl-2'-nitro-[1,1'-biphenyl]-2,6-dicarboxylic acid esters].
Hydrolysis of the dienamine function of the dihydrobiphenyls 3 leads to a mixture of the tautomers 4A-C (NMR). The structures of the starting material 3a and the products 4cA and 4bC are confirmed by X-ray crystal analysis. The biphenyls 5 are formed by dehydrogenation of 3 with iodine, whereas 4b produced the additional iodinated compound 6. 4b reacts with manganese dioxide to yield the phenol 7a. Irradiation of the dihydrobiphenyls 3 with UV-A light gives the nitrosobiphenyls 8. In contrast, the nitrobiphenyl 7b and the lactam 10a are formed as photo products from 4c. The reduction of the nitro group of 5 with Fe/AcOH leads to the isomeric phenanthridines 10 and 11 by cyclization, whereas after reaction with Zn/NH4Cl the cyclic hydroxamic acids 12 and 13 are isolated. Compound 7a reacts with Zn/acetate buffer to yield only the hydroxamic acid 12. Ring closure takes place on treating the nitrosobiphenyls 8 with conc. hydrochloric acid, to yield the chloro-substituted hydroxamic acids 14. The half wave potentials of the dihydrobiphenyls 3 and 4 are measured by anodic oxidation using a rotating platinum electrode by means of differential pulse voltammetry. The dienamines 3 are more sensitive towards oxidation than the reference drug nifedipine; in contrast, the carba-analogues 4 are much more stable. The cyclic hydroxamic acids 13 and 14a are tested for their ability to inhibit 5-, 12- and 15-lipoxygenase. Compound 13 represents a weak inhibitor of 5-lipoxygenase in human whole blood.
Görlitzer
K
K
Institut für Pharmazeutische Chemie der Technischen Universität Braunschweig, Germany. k.goerlitzer@tu-bs.de
Trittmacher
J
J
Jones
P G
PG
Frohberg
P
P
Drutkowski
G
G
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D016861:Cyclooxygenase Inhibitors; D007202:Indicators and Reagents; D010617:Phenanthridines