Penicillium griseofulvum Dierckx

Griseofulvin, an antibiotic produced by the mold Penicillium griseofulvum (Dierckx), has been synthesized by a route that employs a twofold Michael reaction as the key step. Propose a mechanism for this transformation. 

The mold metabolite mycelianamide, isolated from the mycelium of strains of Penicillium griseofulvum Dierckx, was first investigated by Oxford and Raistrick24. The reinterpretation and extension of this work by Birch etal.2 and the revision by Bates et al.20 of the structure first proposed for the terpenoid side-chain,25 have led to the formulation of mycelianamide as 11. This structure has been confirmed by further degradations27,28 and by a synthesis of racemic deoxymyceli-anamide by Gallina and co-workers.28 The ready decomposition of the heterocyclic ring by either acid or alkali is discussed later (Section IV, C). 

Griseofulvin [XLIX], first isolated from Penicillium griseofulvum Dierckx, is effective orally in the treatment of ringworm in animals and man. The observations of Gentles , and Cochrane and Tullett , in antifungal experiments, that this antibiotic seems to possess anti-inflammatory properties led... 

CO2H Penicillium griseofulvum Dierckx CSIR 1082 complete retention of tritium... 

Using the above assignments, these workers fed [1,2- 2]acetate to Penicillium griseofulvum Dierckx and determined that the Z-methyl group (C-22) in j9-cyclopiazonic acid becomes the )0-methyl group (C-22) in a-cyclopiazonic acid (Scheme 51). 

Birch, A. J., R. A. Massey-Westropp, and C. J. Moye Studies in relation to biosynthesis VII. 2-hydroxy-6-methylbenzoic acid in Penicillium griseofulvum Dierckx. Australian J. Chem. 8, 539 (1955) ... 

Oxford, A. E., H. Raistrick, and P. Simonart Studies in the biochemistry of micro-organisms. LX. Griseofulvin, Ci7Hi-OeCl, a metabolic product of Penicillium griseofulvum Dierckx. Biochem. J. 33, 240 (1939). 

Simonart, P., A. Wiaux and H. Verachtert Etude biochimique de Penicillium griseofulvum Dierckx. II. Formation d acides dihydroxybenzoiques. Bull. soc. chim. biol. 41, 541 (1959). 

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