Natural Products Originated from the Oxidative Coupling of Tyrosine and Tryptophan: Biosynthesis and Bioinspired Synthesis

Abstract

The oxidative coupling of tyrosine and tryptophan units is a pivotal step in the total synthesis of some peptide‐derived marine and terrestrial natural products, such as the diazonamides, azonazine and tryptorubin A. This Minireview details the biosynthesis and bioinspired synthesis of natural products with such structures. A special focus is put on the challenges of the synthesis of these natural products and the innovative solutions adopted by synthetic chemists.

The tryptophan connection: cyclic peptide natural products linkedviathe tryptophan side chain

“…A common linkage observed in tryptophan-linked peptide natural products is carbon–carbon bond formation between the indole carbocycle and another electron-rich aromatic ring. 10 This motif is a key structural feature of the complestatin-like natural products (Fig. 10).…”

“…9 In 2021, Tang and Vincent published a review of natural products formed from the oxidative coupling of tyrosine and tryptophan, with a focus on their biosynthesis and bioinspired chemical synthesis. 10 Our review represents the first comprehensive report on the isolation, bioactivity, and where completed, total synthesis of cyclic peptide natural products linked by tryptophan. Additionally, progress towards understanding the biosynthesis of these compounds is discussed.…”

Hypervalent Iodine‐Mediated Late‐Stage Peptide and Protein Functionalization

“…Theo xidation of Ty rr esidues using PIDA( 5)h as been also used for intramolecular coupling with Tr pt os ynthesize natural products. [44]…”

Metal‐Catalyzed C(sp2)−H Functionalization Processes of Phenylalanine‐ and Tyrosine‐Containing Peptides

“…Driven by the exponential growth of C(sp 2 )−H functionalization reactions within simple aryl systems, a variety of site‐selective methods for the modification of aromatic residues such as tryptophan (Trp) [9] have been devised by harnessing the innate reactivity of its indole ring. Indeed, the oxidative coupling of Trp and tyrosine (Tyr) residues constitutes a crucial step within the biosynthesis of a sheer number of natural products [10] . In stark contrast, the modification of typically inert C(sp 2 )−H bonds within phenylalanine (Phe) has been overshadowed and comparatively less studied [11] .…”