Studies in the biochemistry of micro-organisms

Abstract

cf. C. A. 29, 5837.8; 33, 4287.6. Griseofulvin (I), m. 218-19°, [α]546119° 417°, was isolated from a culture of P. griseo-fulvum grown on media contg. glucose as the sole source of C. I contained 3 MeO groups, one being part of an ester group, a keto group and probably an O bridge. Oxime of I, m. 226-7°. Hydrolysis of I with N aq. alc. H2SO4 gave griseofulvic acid (II), C16H15O6Cl, m. 256-60°, [α]546119° 508°. Hydrolysis of I or II with hot 0.5 N NaOH gave norgriseofulvic acid (III), C15H13O6Cl, m. 260°, [a]546118°, 609°, and decarboxygriseofulvic acid (IV), C15H15O4Cl, m. 138-40°, [α]546118° -31°. III contained a phenol group and titrated as a dibasic acid. IV was neutral and stable to acid hydrolysis. Methylation of II or III with CH2N2 gave I and isogriseofulvin, m. 198-200°, [α]546119° 265°. The catalytic reduction of I with Pd and H formed dihydrogriseofulvin, C17H19O6Cl, m. 194-6°, [α]546118° -33°, and tetrahydrogriseofulvin, C17H21O5Cl, m. 180°, which no longer gave keto reactions. The oxidation of I, II, or III in Me2CO with KMnO4 produced 3-chloro-2-hydroxy-4,6-dimethoxybenzoic acid, m. 224°. A 2nd acid (V) was formed from I and II by oxidation. V, C14H15O7Cl, m. 200°, [α]579018° -24°, contained a keto group. V reacted with Ac2O in C5H5N to give a neutral substance, C14H13O6Cl, m. 220°. Fusion of I with KOH gave orcinol. A tentative formula is suggested for I on the basis of the reactions studied. [on SciFinder(R)]