|Keywords (Extracted from title, table of contents and abstract of thesis)
penicillin funiclosum-thom, funiculosic acid, mold metabolites, metabolic products, czapeck-dox medium, crystalline metabolites, mycelium, ergosterol, mannitol
Penicillium Funiculosum-thom when grown on Czapeck-Dox medium enriched with carrot extract was shown to produce crystalline metabolites which have not been previously described from this mold in the literature.
From the mycelium, ergosterol and mannitol have been isolated. In view of the importance of ergosterol as a precursor in the synthesis of vitamin D2, conditions conducive to maximum production of ergosterol have been investigated.
The ethyl acetate extract of the broth was resolved into neutral fraction (A) and acidic fraction (B). The neutral fraction (A) on removal of solvent, furnished diethyl phthalate, b.p. 295oC. The aqueous alkaline layer (Fraction B) on acidification afforded a crystalline acid, C9 H8 O5 (M+ 196) m.p. 260oC (dec.) for which the trivial name funiculosic acid has been proposed, on the basis of chemical and spectral evidence, funiculosic acid was formulated as 2-formyl-3, 5-dihydroxy p-toluic acid XVII, It has been shown that funiculosic acid exists predominantly in open from due to strong intra-molecular hydrogen bonding between the –CHO and the adjacent phenolic –OH groups.
Funiculosic acid furnished methyl ester XVIII, m.p. 170oC (M+ 210); ethyl ester, XIX, m.p.165oC (M+ 224). Whereas acetylation on ethyl ester XIX afforded ethyl-O, O-diacetyl funiculosate XX, C15 H16 O7. m.p. 92oC, funiculosic acid XVII on acetylation under similar condition, furnished 3,4,6-tri abetoxy-5-methyl phthalide XXII C15 H14 O8 m.p. 195oC (M+ 322).
Methtylation of funculosic acid XVII with CH3I/K2CO3 (anhyd) yielded 4,6-dimethoxy-3-hydroxy-5-methyl phthalide XXIII, C11 H12 O5 m.p. 173oC which on reduction with zinc/sulfuric acid furnished 4,6-dimethoxy-5-methyl phthalide XXXVI. m.p. 154oC. Alkali fusion of funiculosic acid resulted in the isolation of 3,5-dihydroxy-p-toluic acid XXIX.
Funiculosic acid XVII on heating above its melting point dimerizes to give 1,3,5,7, tetrahydroxy-2,6-dimethyl-4, 8-diformyl anthraquinoone, XXXVIII.
An unambiguous synthesis of funiculosic acid XVII has also been described. The key step in the synthesis was formylation of methyl 3,5-dihydroxy-p-toluate XXX employing Gattermann’s conditions to give methyl ester XVIII which on hydrolysis garnished funiculosic acid XVII.