Stipitatic acid

Cook has suggested that colchicine itself may contain the 7-membered ring B and Dewar has proposed for the alkaloid formula (XV) with (XVfl) as a resonance form, mainly on the ground that the third ring (C) in colchicine resembles in some of its reactions, stipitatic acid and presents similar difficulty in interpretation of experimental results. 

Numerous reactions of the betaines 86 with olefinic 1,3-dipolarophiles have been reported. lV-Methylpyridinium-3-olate (111) with electron-deficient olefins gives the adducts 112. - Alkynes give similar adducts (110) These adducts (110 and 112) are useful intermediates for tropolone synthesis. Quaternization to methiodides (113, 115) and treatment with base gives dimethylaminotropones (114) which are hydrolyzed to tropolones (116). Good syntheses of stipitatic acid (116 R = COjH, R = OH) and hinokitiol (116 R = H, R = CHMe ) have been achieved by this route (Scheme 5). Similar transformations have been achieved using the N-phenyl betaine 86 (R = Ph, R = H) which is more reactive but whose adducts are difficult to quaternize. A difference is observed when benzyne is... 

The mold metabolite stipitatic acid was synthesized in seven steps from 2,3-dimethoxycarbonyl-1,4-benzoquinone, via a thermal cyclopropyl anion rearrangement of 7 to 8 as the key step. ... 

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). 

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... 

A new synthesis of tropones has been announced which involves cyclocoupling of polybromo-ketones and 1,3-dienes, promoted by iron carbonyl. Stipitatic acid and hinokitiol have been made by a novel procedure involving intermediates (1) and (2) followed by Hofmann elimination of the bridge in (2). 

As pointed out by Andrew and Segal (1964), different strains of P. cyclopium elaborate puberuHc acid, orsellinic acid, cyclopohc and cyclopaldic acids. A biological connection between the latter three compounds and the tropolones has, however, not yet been fixed. The participation of orseUinic acid in stipitatic acid remains especially equivocal experiments to test the conversion of radioactive orsellinic acid or orcylaldehyde into stipitatic acid were negative (Bentley,... 

Andrew, I. G., and W. Segal Mould tropolones Biosynthesis and alkah-isomeri-zation of stipitatic and decarboxylated stipitatic acid. J. Chem. Soc. 1964, 607. 

Bentley, R. Aromatic synthesis in molds formation of the tropolone stipitatic acid. Biochim. et Biophys. Acta 29, 666 (1958). 

Bentley, R. Biosynthesis of tropolones in Penicillium stipitatum II. The degradation of C -labeled stipitatonic and stipitatic acids. J. Biol. Chem. 238, 1889 (1963 a). 

Birkinshaw, J. H., A. R. Chambers, and H. Raistrick Studies in the biochemistry of microorganisms. 70. Stipitatic acid CgHgOg a metabolic product of Penicillium stipitatum Thom. Biochem. J. 36, 242 (1942). ... 

Divekar, P. V., P. E. Brenneisen, and S. W. Tanenbaum Stipitatic acid ethyl ester a naturally occurring tropolone derivative. Biochim. et Biophys. Acta 50, 588 (1961). 

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