Novel photodegradation of the antifungal antibiotic pyrrolnitrin in anhydrous and aqueous aprotic solvents.
The UV irradiation of pyrrolnitrin (1a), which is an antibiotic clinically useful against dermatophytosis and possesses a unique 2-(pyrrol-3-yl)nitrobenzene moiety in the molecule, in an anhydrous aprotic solvent resulted in the exclusive formation of transient 7,4'-dichlorospiro[1,3-dihydrobenzo(c)isoxazole-3,3'-pyrrolin-2'-one] (2a) via the intramolecular oxidation of the juxtaposed pyrrole ring by the triplet-excited nitro group. The irradiation in an aqueous aprotic solvent, however, allowed the concurrent occurrence of intramolecular cyclization by the singlet-excited nitro group in 1a and the hydroxylation at the 2-position of the pyrrole ring by water to afford 3,7-dichloro-8-hydroxy-8,8a-dihydropyrrolo[2,3-b]indol-2-one (3a), accompanied by the formation of 2a. Elongation of the irradiation time in these photoreactions caused a rapid consumption of the products, 2a and 3a, to give undetermined polar polymeric products. The present results indicate that the photodegradation of 1a is significantly influenced by the presence of water in the reaction media and by the nature of its excited state. Thus, the loss of the antifungal activities by the photosensitive antibiotic 1a was chemically proved.
Sako
Magoichi
M
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan. sako@gifu-pu.ac.jp
Kihara
Toshiyuki
T
Tanisaki
Mihoko
M
Maki
Yoshifumi
Y
Miyamae
Akira
A
Azuma
Toshio
T
Kohda
Shigetaka
S
Masugi
Takashi
T
D000935:Antifungal Agents / Q000737:chemistry*; D015394:Molecular Structure; D010777:Photochemistry; D011764:Pyrrolnitrin / Q000737:chemistry*; D012997:Solvents; D013057:Spectrum Analysis; D014867:Water
D000935:Antifungal Agents; D012997:Solvents; D014867:Water; D011764:Pyrrolnitrin