Modern Synthesis of the Isocyanides

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. 

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. 

In 1957, Ugi et al. compared the spectroscopic data of comparable tetrazole and penta-zole derivatives [56], and noted that the 1-substituted tetrazoles were easily produced from isocyanides and hydrogen acid [29], but that the desired isocyanides were less easily prepared. Ugi then successfully investigated the formation of isocyanides by dehydrating 

An increasing number of different isocyanides was produced, such that 329 known isocyanides were described in Isonitrile Chemistry in 1971 [8]. By comparison, during the era of classical isocyanide chemistry before 1960, only about 12 isocyanides were known. 

It was then also recognized [61] that many isocyanides - especially the di- and tri-iso-cyanides - have plant-protecting and antibiotic properties. Moreover, it was also realized that these properties remained active, even after 200 generations. 

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