Carolic acid

Baldwin, Carol. Acids and Bases. Austin, Tex. Raintree Publishers, 2005. 

Following the discovery that carolic acid exists in trichloromethane solution as the cyclic anhydride in a mixture of geometrical isomers, it has been shown that the compound crystallizes from ethanol as the ( )-isomer (72). 

Before its true nature as a vitamin deficiency disease was firmly established, a connection was made between the incidence of pehagra and the consumption of mouldy maize. Several Penicillium species were isolated from this source. Examination of one of these, P. charlesii, by Raistrick between 1933 and 1935 led to the isolation of a series of acidic metabohtes that were derivatives of tetronic acids and exemplified by L-y-methyltetronic acid (6.11), carolic acid... 

Biosynthesis of carolic acid in Penicillium charlesii, J.L. Bloomer, F.E. Kappler and G.N. Pandey, Chem. Commun., 1972, 242. 

The fungal metabolites patulin (10) and multicolic acid (79) are derived in nature via oxidative cleavages of polyketide derived aromatic intermediates a similar pathway has been established for the tetronic acid penicillic acid (185). By contrast, the biosynthesis of carolic acid (76a) which is found with dehydrocarolic acid (75) in P. charlesii, has been shown to occur from Krebs cycle intermediates. 

The biosynthesis of the fungal tetronic acids penicillic acid (185) and carolic acid (76 a), which are closely related structurally to patulin and multicolic acid, have also been studied extensively. Early work with " C-labelled precursors has clearly demonstrated the polyketide origin of penicillic acid, and also the intermediacy of orsellinic acid... 

The biosynthesis of the fungal tetronic acid carolic acid (76 a) in Penicillium charlesii is markedly different from that of patulin, multicolic acid and penicillic acid. Carbon-14 work has demonstrated that the carbon sub-unit C-3, C-4, C-9 in the acid is derived from a C-4-dicarboxylic acid such as succinate, whereas the remaining six carbons (C-1, C-2, C-5, C-6, C-7, C-8) are derived from two malonate units (C-5, C-6, C-7, C-8) and just one acetate unit (C-1, C-2) (Scheme 19) (775). It is proposed then that the biosynthesis of carolic acid proceeds from a C4-dicarboxylic acid first to either y-carboxymethyltetronic acid (196) or to carlosic acid (77 b) hydroxylation of carlosic acid then gives rise to carlic acid (77 a) which on decarboxylation produces carolic acid 176). 

Bentley, R., D. S. Bhate, and J. G. Keil Tetronic Acid Biosynthesis in Molds 1. The Formation of Carlosic and Carolic Acids in Penicillium charlesii. J. Biol. Chem. 237, 859 (1962). 

Bloomer, J. L., F. E. Kappler, and G. N. Pandey Biosynthesis of Carolic Acid in Penicillium charlesii The Intermediate Precursors. Chem. Commun. 243 (1972). 

Syntheses, published in 1976, of naturally occurring tetronic acids include those of (S )-carlosic acid (75) and the related (/ )-carolic acid and of fungal pigments based on the pulvinone e.g. 76) and pulvinic acid e.g. 77) structures. 

Car-3-ene, A35 Car-4-ene, T5 /raw5-car-4-ene-3- ol, T6 Caracurine VII, K12 fraw5-caran-2-one, T6 Caranes, T6 Caranine, K6 Carbodiimides, X3 Carbomycin, Y25 Carbonates, A14-15 Carbonyls, X9, X2, Zl / -carboxybutyramide, A34 Cardenolides, T49 Cardiolipin, A15 Carlosic acid, A12 Carminomycin, Y28 Carnitine, A2 Carnosine, A20 Carnosol, T33 Carolic acid, A12 ... 

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