Katsuhiko Kitahara

Quantitative structure-activity studies of benzoylphenylurea larvicides: II. Effect of benzyloxy substituents at aniline moiety against Chilo suppressalis Walker

Abstract The larvicidal activity of a series of N -2,6-difluoro- and N -2,6-dichlorobenzoyl- N′ -(4-substituted phenyl)ureas against nondiapause larvae of the rice stem borer, Chilo suppressalis Walker, was measured by topical application and oral administration methods under conditions with and without piperonyl butoxide as an inhibitor of oxidative metabolism. The effects of substituents at the anilide moiety on the larvicidal activity were analyzed quantitatively using physicochemical substituent parameters and regression analysis. The results indicate that the oxidative metabolism in the larval body which is favored by electron-donating substituents is significant in determining the activity. The activity, when the metabolic factor is eliminated, is enhanced by electron-with-drawing and hydrophobic substituents and lowered by bulky groups. The inhibitory activity against new cuticle formation of the same series of compounds was also measured using cultured integument of the rice stem borer diapause larva. The comparison of the quantitative analyses between larvicidal and integument-level activities shows that inhibition of cuticular development is the most important factor governing larvicidal activity.

Quantitative structure-activity studies of benzoylphenylurea larvicides: III. Effects of substituents at the benzoyl moiety

Abstract The larvicidal activity of 2-substituted- and 2,6-disubstituted-(4-chlorophenyl)ureas against rice stem borers (Chilo suppressalis) and silkworms (Bombyx mori) was measured by topical application under conditions in which oxidative metabolism was eliminated using piperonyl butoxide. The substituent effects at the benzoyl moiety on the activity were analyzed quantitatively using physicochemical parameters and regression analysis. The substituent parameter for the electron withdrawal from the side chain was estimated taking into consideration the steric inhibition of the resonance of ortho substituents. The results indicated that the larvicidal activity was enhanced by electron-withdrawing and hydrophobic substituents and lowered by bulky groups. The effect of substituents at the benzoyl moiety on activity was about the same for rice stem borers and silkworms. In vitro inhibition of the same series of compounds against new cuticle formation was also measured using cultured pieces of integument of diapause larvae of the rice stem borer. In vitro activity was linearly related to in vivo activity after allowing for the hydrophobic factor that may contribute to transport.

Syntheses of Ribofuranosyl-2-deoxystreptamines

4-0-, 5-0- and 6-0-β-d-Ribofuranosyl-2-deoxystreptamine derivatives were prepared from 4 (or 6)-O-acetyl-N, N′-dicarbobenzyloxy-2-deoxystreptamine and 2, 3, 5-tri-O-benzoyl-d-ribofuranosyl chloride by a modified Konigs-Knorr reaction. Structures were determined by identification with an authentic sample derived from neomycin for the 5-O-isomer, and by comparison of the Δ [M]CuAm values of their N-acetyl derivatives for the 4-0- and 6-O-isomers.

Total Synthesis of Ribostamycin

Suitably protected 5-O-β-d-ribofuranosyl-2-deoxystreptamine was condensed with protected 2, 6-diamino-2, 6-dideoxy-a-d-glucopyranosyl bromide by a modified Konigs-Knorr reaction to give three condensation products. One of which was confirmed as a ribostamycin derivative. The others were designated as its 6-O-α- and 6-O-β-isomers by the PMR spectra of their free bases and N-acetyl derivatives and by their chemical reactions.

Synthetic Studies on Carbohydrate Antibiotics: Part X.1) Synthesis of Methyl Kasugaminide

Methyl N, N′-diacetyl-α-kasugaminide and its C4 epimer were synthesized starting from d-glucose, and their configurations were discussed.