Xanthocillin

Formerly, isonitriles were perhaps best known to many chemists through the indescribably vile odor of volatile members of the series encountered during the Hofmann carbylamine test for primary amines. Over recent years, however, isonitriles have come into their own as versatile synthetic reagents. Several reliable preparative methods now allow ready access to this family of substances and their remarkable chemistry. Biological pathways to isonitriles are also known, the first such substance isolated being the antibiotic xanthocillin (141), isolated from Penicillium notatumP Isonitrile compounds are also isolated fairly frequently from marine sources. ... 

A new xanthocillin 80 was isolated from marine fungus Basipetospora sp. as thrombopoietin (TPO) mimics. It promoted the proliferation of a TPO-sensitive human leukemia cell line, UT-7/TPO, and UT-7/EPO-mpl, genetically engineered to express c-Mpl, a receptor for TPO in dose-dependent manners. However, the proliferation of UT-7/EPO, a parental cell line of UT-7/EPO-mpl that was devoid of TPO receptor, was not affected by it. These data indicated that xanthocillin 80 is putative agonists for c-Mpl, as its cellular actions was analogous to those of TPO. 

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. 

The O.O -dimethyl-Xanthocillin 28 was prepared from its N, N -diformyl-diamine 27. This was dehydrated by phenyl-sulfonyl-chloride in the presence of pyridine. The procedure was published in Pharmazie [53] in East Germany in 1956, but was not available to Western countries. The method can be used particularly if isocyano-polymers are formed [54]. Two years later, Hertler and Corey [55] reported a similar conversion of a formyla-mino-steroid into its isocyano-derivative. 

The last step of the synthesis of the antibiotic xanthocillin by Hagedom in 1956 is the first published synthesis of an isocyanide (2) by dehydration of an A -monosubstituted formamide (1). 

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 Xantocillin Brevicid. Antibiotic complex produced by Peniciltium notatum Westling Rothe, Pharmazie 5, 190 (1950) Barwald, Brit. pat. 890,498 (1962 to Arzndmittelwerk VEB), C.A. 57, 9013a (1962). Consists of at least three antibiotics, xanthocillins X Yj and Y2 the first being the major component (about 70%). 

The hazimycins appear to be derived by simple coupling of two tyrosine residues ortho to the hydroxyl groups. Again the origin of the isonitrile function is unclear. In contrast to the situation for xanthocillins, [Me- CJ-methionine did act as a precursor, albeit considerably less efficiently than tyrosine and feeding of the C-labelled compound proved that the methyl group labelled the isonitrile function. Thus formation of the latter by oxidation of a N-methyl group seemed likely but, inconsistently with this, no label... 

Xanthocillin-X, a typical metabolite of this group, was first isolated from Pen. notatum as an antimicrobial principle (255). The structure was elucidated by Hagedron and Tonjes (256) to be l,4-di(p-hydroxyphenyl)-2,3-diisocyano-l,3-butadiene (172). Acid hydrolysis of 172 affords l,4-di(p-hydroxyphenyl)-... 

Xanthocillin-X monomethylether (XME), dimethylether (XDE), and itiethoxy xanthocillin-X dimethylether (XTE) have been isolated from Dendotomyces albus and from two strains of Asp. chevalieri by Suzuki and co-workers (258). All these compounds decompose near 183°C and are effective against Newcastle disease and inhibit the growth of Bacillus subtilis. XME specifically inhibits the conversion of arachidonic acid to prostaglandin H2 (259) and shows an inhibitory activity against platelet aggregation. 

C20H16N2O2, Mr 316.36, greenish-yellow cryst., mp. 225-226 °C. Dinitrile from cultures of Aspergillus nidulans with structural similarity to diisonitriles of the xanthocillin type. 

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