763. Griseofulvin. Part V. Catalytic reduction

Abstract

Hydrogenation of griseofulvin may take three routes, viz. : ( a ) reduction of the double bond only, to givc a product which on further hydrogenation undergoes reduction of the reactive keto-group and hydrogenolysis of the chlorine ; (b) reduction to an alcohol and saturation of the ethylenic linking ; or (c) reduction of the keto-group to an alcohol group which is hydrogenolysed to methylene, followed. by reduction of the ethylenic linking. Hydrogenation of isogriseofulvin follows mainly route (b) . THE present paper describes the reduction of griseofulvin (I) and isogriseofulvin (VI).The chemistry of the products is described in Part VI (following paper).GriseofuZvin.-In the first two experiments with palladised charcoal, reduction was slow, as described by Oxford, Raistrick, and Simonart (Biochein. J., 1939, 33, 240), giving dihydrogriseofulvin Cl,H1,O,C1 (40 yo) , and tetrahydrodeoxygriseofulvin C1,H210,CI * Part IV, preceding paper.

Synthesis and Structure−Activity Relationship of Griseofulvin Analogues as Inhibitors of Centrosomal Clustering in Cancer Cells

“…Analogue 27 was available by reduction of 1 with hydrogen catalyzed by platinum on charcoal, an improvement of a published procedure. 21 The oximes 28 and 29 were derived from the parent ketones by treatment with hydroxylamine hydrochloride in ethanol and DMSO, a slight modification of the method of Delgado et al 17 and isolated as inseparable 1:1 mixtures of geometrical isomers. In a similar fashion, the hydrazine 30 was synthesized by heating 1 with N,N-dimethyl hydrazine and acetic acid in toluene.…”

“…The 4′ alcohol 26 was derived from 1 using a slight modification of a known method (Scheme ). Analogue 27 was available by reduction of 1 with hydrogen catalyzed by platinum on charcoal, an improvement of a published procedure . The oximes 28 and 29 were derived from the parent ketones by treatment with hydroxylamine hydrochloride in ethanol and DMSO, a slight modification of the method of Delgado et al and isolated as inseparable 1:1 mixtures of geometrical isomers.…”

On the Polarographic Reduction of Griseofulvin and Some of its Derivatives

“…OR II It appears that the carbonyl group at ring C of 1 undergoes reduction prior to the ethylenic linkage. This is also the case in the catalytic reduction of I (Pd/c) [6] .…”

Synthesis and Biological Activities of Griseofulvin Analogs

“…9 ) Antimicrobial assay of the griseofulvin analogs (3--8) against Botrytis allii (IFO 9430) and Botrytis cinerea (AHU 9573). The antimicrobial activity of the synthesized analogs was determined by the paper disc method in potato sucrose medium.…”

“…Griseofulvin as a standard was employed for comparision purposes in this test. Compounds 9 and 10 prepared from 1 by the known method 9 ) were also tested to compare with the activity of (± )-3--8. the antimicrobial activity was determined by a paper disc method, the activities of the test compounds being listed in Table II. (±)-6'-Demethyl analog 3 showed quite weak activity, and 4'-deoxo analog 10 did not show any activity. The activities of (±)-5 and (±)-7 were considerably inferior to that of 1.…”