759. Griseofulvin. Part I

Abstract

The structures proposed for griseofulvin, C17H1706Cl, by Oxford, Raistrick, and Simonart (Biochem. J., 1939, 33, 240) and by Grove and McGowan (Nature, 1947, 160, 574) are inconsistent with the ultra-violet and infra-red absorption spectra. Grove and McGowan's suggestion (Chew. and Ind., 1949, 647), based on spectroscopic data, that griseofulvin is the methyl ether of a 1 : 3-diketone has been proved conclusively by catalytic reduction of griseofulvic acid, Cl,H ,O,Cl, to two neutral non-lactonic alcohols, C,,Hl,O,C1 and C,,Hl,O,Cl, and by other evidence. The formation of decarboxygriseofulvic acid by the action of alkali on griseofulvic acid is shown by ultra-violet and infra-red spectroscopic evidence to involve a rearrangement of the molecule. GRISEOFULVIN, C,,H,,O,Cl, m. p. 220°, [a]:& +354", a colourless neutral compound containing three methoxyl groups, was isolated from the mycelium of Penicilliuutz griseofuluum Dierckx by Oxford, Raistrick, and Simonart (Biochem. J., 1939, 33, 240). Subsequently, it was isolated from P. jnnczeuskii Zal. [= P. nigricans (Bainier) Thom] and its unique biological activity on moulds noted by Brian, Curtis, and Hemming (Trans. Brit. 2tlycoZ. SOC., 1946, 29, 173; see also Brian, A m . Bat., 1949, 13, 59) and McGowan (Trans. Brit. Mycol. SOC., 1946, 29, 188) who originally called it ' I curling factor " before the identity with griseofulvin was established (Grove and McGowan, Nature, 1947, 160, 574; Brian, Curtis, and Hemming, Trans. Brit. Mycol . SOC., 1949, 32, 30).Although the chemical and biological properties of ' I curling factor " and griseofulvin were identical, the analytical data and molecular-weight determinations quoted by McGowan (Zoc. cit.) in support of his original formula C,,H,,O, agreed more closely with C,,H,,O,Cl than with C,,H,,O,Cl. However, a careful reinvestigation has established the empirical formula as C1,H,,O,C1, in agreement with the earlier work of Oxford ei al. and this is supported by molecular-weight determinations by both the Rast and crystallographic methods (the latter by Dr. A. F. Wells). Nevertheless, the structure (I) tentatively proposed by Oxford et al. (loc. cit.) is not entirely satisfactory even on the basis of the facts which they reported, and we have accumulated considerable evidence which cannot be reconciled with it. We have repeated practically all the experimental workRecent work on the correlation of absorption frequency and structure for the C=O and -OH stretching vibrations has been summarised by Grove and Willis (J., 1951, 877). Normal carboxylic esters generally absorb between 1715 (conjugated) and 1745 cm.-l (unconjugated). These frequencies may be raised by the presence of powerful electronattracting substituents (e.g., NO,) or lowered by intramolecular hydrogen bonding (chelation) ; however, neither of these complications is present in the griseofulvin molecule. Griseofulvin (Fig. 3b) has no absorption bands in the carboxylic ester range, and the Derivatives. Griseofulvin (0.4 g.) and bromine (0.6 g.) were dissolved ...

Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells

“…Nine of the compounds were active against both fungi within the same order of magnitude compared to griseofulvin (17,20,21,23,26,32,36,49, and 54).…”

Analytical techniques for griseofulvin

“…The method involves solvent extraction of the whole broth sample with butyl acetate and they measured the UV-spectophotometric absorption. Extinction values of griseofulvin at 291 nm in methanol has been reported [7]. The extinction was reported to be high in 0.2% aqueous formamide solution and saturated in benzene.…”

A Rapid Method for the Determination of Griseofulvin in Fermenter Broth

“…OMe and a process for the isomerisation using hydrochloric acid in methanol has been described by Grove, MacMillan, Mullholland and Thorold-Rogers (1952). Griseofulvin and its isomer show significant differences in absorption between 260 and 280 mp ( Fig.…”