Curvularin

Zhan J, Wijeratne EMK, Seliga CJ, Zhang J, Pierson EE, Pierson III LS, VanEt-ten HD, Gunatilaka AAL, A new anthraquinone and cytotoxic curvularins of a Penicillium sp. from the rhizosphere of Fallugia paradoxa of the Sonoran desert, JAntibiot 57 341-344, 2004. 

Kobayashi A, Hino T, Yata S, ItohTJ, Sato H, Kawazu K, Unique spindle poisons, curvularins and its derivatives, isolated from Penicillium species, Agric Biol Chem... 

With complex (102) as catalyst, reaction (107) has been used to prepare a precursor of the natural product curvularin.482 If cyclic ethers are used instead of alcohols, w-haloesters are... 

The Pd(0)-catalysed carbonylation of benzyl chloride proceeds under atmospheric pressure in a two-phase system utilizing the water-soluble phosphine to give phenylacetic acid (461) [227]. In the total synthesis of the macrolide curvularin (465), the Pd-catalysed carbonylation of the benzyl chloride 462 in the presence of the alcohol 463 to give the ester 464 has been applied [228]. Phenylacetic acid (461) is produced commercially by Co2(CO)8-catalysed carbonylation of benzyl chloride. The Co2(CO)8-catalysed double carbonylation of benzyl chloride using Ca(OH)2 as a base gives phenylpyruvic acid (466) with high selectivity [229]. Selection of solvents is important. DME is a good solvent, whereas MeOH is not satisfactory. 

This strategy has been used in the synthesis of the mould metabolite curvularin and its dimethyl ether derivative [146]. In the synthesis of curvularin (242) by Gerlach [146a], carboxylic acid 240 was exposed to a mixture of trifluoroacetic acid and its anhydride to give the macrocycle 241 via a Friedel-Crafts acylation. 

A mechanistically related and mild fragmentation is that of 2-trimethylsilylethyl esters (Tmse esters). The Tmse residue is a selectively cleavable carboxy-protecting group (see Volume 6, Chapter 3.2) Examples are known for the synthesis, via these esters, of peptides, macrolides such as curvularin and macrocyclic trichothecenes like verrucinol (Scheme 54). °... 

Simple Monocyclic Macrolides A. Recifeioltide Diplodialides Lasiodiplodin Curvularin Zearalenone Brefeldin A... 

Curvularin (107) is a 12-membered ring keto lactone containing a fused 1,3 dihydroxybenzene ring. This mold metabolite, isolated from the extracts of the Curvularia species and Penicillium steckii, has some rather unexpected chemistry associated with it. ... 

Brefeldins A (4.104) and B, obtained from Penicillium brefeldianum and which also possess a cyclopentane ring, have a wide spectrum of biological activity, including antiviral and cytotoxic effects. Brefeldin A has been shown to incorporate acetate and specifically [9- C]palmitic acid, suggesting that it is biosynthesized by a fatty acid pathway. However, other macrolactones such as curvularin appear to be biosynthesized by a polyketide pathway. 

A new polyketide, 14,15-secocurvularine (48), was isolated from the salt culture of an unidentified fungus obtained from an Indo-Pacific sponge, Spirastrella vagabunda, and identified by the usual spectroscopic methods. This substance is related to curvularine, which has been reported from different fungi such as Curvularia, Cochliobolus, Penicillium or Altenaria. In biosynthetic terms, secocurvularin would appear to derive from curvularin by an unusual carbon-carbon bond break between C14 and Cl5 [86]. 

This protecting group has been used in a synthesis of the mold metabolite curvularin (6), shown briefly in scheme (I). The intermediate (3) contains two different ester groups, but only the desired group is cleaved by fluoride ion to give... 

---