243. Griseofulvin analogues. Part III. Halogen derivatives of griseofulvin

Application of Fluoroxy Compounds to Organic Synthesis: Electrophilic Fluorination of Unsaturated Molecules

“…'9It is notable that in the transformation 20 to 21 (which attended a parallel aromatic substitution, vide infra) a substitution rather than addition reaction has been observed. Reaction of griseofulvin (20) with bromine or chlorine" affords similar substitution products strengthening the parallel between the reactions of fluoroxy reagents and other halogens. From the foregoing reactions, it is clear that CF,OF reacts with a variety of enolic derivatives or other activated olefins to afford fluorinated products best rationalized as arising from attack of the fluorinating agent upon the most electron-rich terminus of an unsaturated link.…”

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

“…22 Treatment of 1 with N-iodosuccinimide (NIS) and triethylsilyl triflate (TESOTf) afforded 33, and the 3′-iodo analogues 34 and 35 were obtained using the same convenient conditions. This type of compounds have previously been prepared by treating 2 with iodine monochloride and 2 equiv of KOAc, 23 followed by reacting the intermediate with an excess of an appropriate diazo alkane. 24…”

The Chemistry of Griseofulvin

“…43 Position 3′ was the initial halogenation site on griseofulvic acid 78 with either chlorine in carbon tetrachloride or bromine and iodine, respectively, in DMF. 43 Bromination of the 5 position could be done directly on griseofulvin 1 with bromine and mercury(II) acetate yielding 87a (Scheme 18). 43 Scheme 25.…”

“…or bromine and iodine respectively in DMF. 43 Bromination of the 5 position could be done directly on griseofulvin 1 with bromine and mercury(II) acetate yielding 87a (Scheme 18). 43 In 1972 Arkley et al also demonstrated that the nitro functionality could be reduced with iron in acetic acid yielding the 5-amino analog 89 (Scheme 19).…”

“…43 Bromination of the 5 position could be done directly on griseofulvin 1 with bromine and mercury(II) acetate yielding 87a (Scheme 18). 43 In 1972 Arkley et al also demonstrated that the nitro functionality could be reduced with iron in acetic acid yielding the 5-amino analog 89 (Scheme 19). 46 MacMillan had originally discovered that dechlorination of position 7 occurred during reduction of griseofulvin 1 with hydrogen in the presence of palladium on charcoal, with concomitant reduction of the C ring alkene.…”