Puberulic acid

The fungal tropolones puberulic acid (4.29) and stipitatic acid (4.30) were isolated from P. puberulum and P. stipitatum by Raistrick in 1932 and 1942, respectively. Their structures were not established at that time despite extensive chemical degradation. The tropolone structure for stipitatic acid was proposed by Dewar in 1945 and that for puberulic acid in 1950 by Todd. These structural proposals played an important part in the development of ideas of aromaticity. The biosynthesis of these tropolones involves the ring expansion of an orsellinie aeid via stipitatonic acid (4.31). 

The genesis of the tropolone ring was more problematic. Tracer studies on simple mold tropolones such as puberulic acid (CXII) (66) and stipita-tic acid (CXIII) (67) have indicated that these compounds are at least partly derived from acetate. However, sodium acetate-l- C was found (6, 61) to be incorporated entirely into the A-acetyl function of colchicine and not at all into demecolcine (6). 

Among the tropolone compounds found in nature are four tropolone-carboxylic acids,obtained from mold cultures.Two ofthese,stipitatonicadd(CXIV,R = COOH) and stipitatic acid (CXIV, R = H) have been obtained from Penicillium stipitatum (Bentley and Thiessen, 1963). Puberulonic add (CXV, R = COOH) and puberulic acid (CXV, R = H) were obtained from P. aurantio-virens, P. puberulum and P.johan-nioli as well as from strains of the P. cyclopium-viridicatum series (sources quoted in this paper). The infrared spectrum of the sodium salt of the anhydride of stipitatonic... 

The same research group has also re-investigated the biosynthesis of puberulonic (37) and puberulic acid (38) in P. aurantio-virens (NRRL 2138) and have shown that C-9 of (37) is derived from acetate. A common biosynthetic route has been suggested for the fungal tropolones (35)—(38), although attempts to demonstrate the conversion of stipitatonic acid (35) or 3-methylorsellinic acid (33) into puberulonic acid (37) were unsuccessful. ... 

Birkinshaw, j. a., and H. Raistrick Studies in the biochemistry of microorganisms. 23. Puberulic acid C HsOg and an acid CgH Og, new products of the metabolism of glucose by P. puherulum Bainier, P. aurantio-virens BioMrge. Biochem. J. 26, 441... 

A red or brown color obtained when ferric chloride is added to the culture solution indicates the possible presence of one or more of the following substances citrinin, fumigatin, kojic acid, puberulic acid, and puberu-lonic acid. 

Natural products containing the tropoloid ring system are not limited to selected alkaloids of the family Liliaceae. Nootkatin and the thuja-plicins, which have been isolated from the family Cupressaceae, are substituted monocyclic tropolones. In addition, the mold metabolites stipitatic, puberulic, and puberulonic acids contain the tropolone ring. It is of interest, then, to consider the possible biogenetic pathways by which this ring system is constructed in nature. 

QUINONES fumigatin, spinulosin, puberulic add (7), and pubenilonic acid (7). 

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