Cyclopeptides chemical synthesis

The Passerini reaction and the Ugi reaction provide a-acyloxyamides and a-acet-amidoamides, respectively. Naturally, these reactions have been applied in the synthesis of peptides and cyclopeptides/cyclodepsipeptides [91]. Recently, the application of these reactions in the synthesis of heterocycles was reported. One of the most notable examples is Fukuyama and co-workers total synthesis of ecteinascidin 743 (Et 743) (148), a complex natural product recently commercialized as an anticancer drug (Scheme 5.46) [92]. Thus, reaction of the amine 149, the amino acid 150, 4-methoxyphenyl isocyanide (151) and acetaldehyde afforded the corresponding Ugi adduct 152 in 90% yield. After a series chemical transformations, 152 was ultimately converted to Et 743. The connection between the structure of Et 743 and the peptidic nature of Ugi adduct is not obvious, but with the deep insight of an experienced synthetic chemist, the non-trivial link can be drawn and be put into practice [93, 94]. 

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