From Isocyanides via Four‐Component Condensations to Antibiotic Syntheses

The four‐component condensation of amines and carbonyl compounds with isocyanides Previously, isocyanides were almost always referred to as isonitriles. However, according to IUPAC Rule C‐833.1 only the name “isocyanides” is permissible. and suitable acid components (water, thiosulfuric acid, hydrogen selenide, hydrogen azide, cyanic acid, thiocyanic acid, carboxylic acids, methyl hydrogen carbonate) to form α‐amino acid derivatives was discovered in 1959. This reaction principle shares some features with the Strecker synthesis and the Passerini reaction. The four‐component condensation affords easy and effective one‐pot synthesis of complex molecules from simple building blocks. Only in recent years, however, have the preparative advantages of the four‐component condensation been exploited by numerous authors in the synthesis of diverse natural products and related compounds, although many of the possibilities opened by this principle were recognized more than two decades ago. In this progress report some instructive syntheses of various antibiotics are reviewed. The design of each of these syntheses involves a four‐component condensation as key step, by means of which lengthy sequences of reactions are avoided, which otherwise would be required to achieve the synthetic goal.