Xanthocillin from Penicillium notatum

In 1948, Rothe [51] discovered the antibiotic xanthocillin, a di-isocyanide which is formed biosynthetically from tyrosine [52] by cultures of Penicillium notatum and Penicil-Hum chrystatum. Presumably, these isocyanide groups are formed by the dehydration of their formylamine groups through the polyphosphate derivatives such as ATP. 

Compounds containing the isocyano group have fascinated natural products chemists ever since the first isocyanide xanthocillin was isolated from the fungus Penicillium notatum Westling in 1950 [1]. The existence of sesquiterpene isocyanides was first reported from the Mediterranean sponge Axinella cannabina in 1973 [2], closely followed by sesquiterpene isocyanides from the Mediterranean sponge Acanthella acuta by Minale et al. [3] and the Hawaiian sponge Halichondria sp. by Scheuer et al. [4]. These early reports also documented the presence of isothiocyanate [2] and formamide [4] functionality attached to the same carbon nucleus as the... 

Xanthocillin (134) is a yellow antibiotic pigment produced by cultures of Penicillium notatum. A novel structural feature , which is of considerable interest from the biogenetic point of view, is the presence of the isonitrile grouping. Because of its symmetrical structure, it has been assumed that the xanthocillin molecule is formed by union of two biogenetically equivalent precursors and tracer experiments performed by Achenbach and Grisebach showed that the Cg.C2 unit was most probably derived from tyrosine. Thus d L-2-[ C]-tyrosine was incorporated into the antibiotic in high yield (25 per cent) and the position of the isotopic label determined by degradation to the a-diketone (135) and anisic... 

The antibiotic xanthocillin X, first isolated from Penicillium notatum by Rothe (1950), was shown to be l,4-di-(/7-hydroxyphenyl)-2,3-diisonitrilo-1,3-butadiene (37) by Hagedorn and Tonjes (1957). Achenbach and Grisebach (1965) and Achenbach and Konig (1971) studied the biosynthesis of this... 

As pointed out before, the isonitrile function is a very rare feature in nature. Until 1973, only the fascinating metabolite xanthocillin, isolated from Penicillium notatum, has been described as a natural isonitrile (7). Very recently the isonitrile function has also been found in four sponge sesquiterpenes. Their structures are shown in Chart 5. 

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