The synthesis of dehydrotryptophan and dehydrotryptophan-containing peptides

Abstract

Dehydrotryptophan and its derivatives are non-proteinogenic amino acids commonly found in peptide-based natural products produced by microorganisms, marine organisms and plants. These non-proteinogenic amino acids are found in secondary metabolites and are formed by post translational modification processes. Although comprehensive reviews on the synthesis of dehydroamino acids are available, this perspective focuses solely on methods to synthesise the dehydrotryptophan-containing segment of naturally occurring peptides, amino acids and their derivatives.

Synthesis of monoalkylidene diketopiperazines and application to the synthesis of barettin

“…Construction of alkylidene diketopiperazines has often been established by combining traditional peptide coupling methods and classic strategies for dehydroamino acid synthesis. 2,3 The synthesis of alkylidene DKPs derived from unnatural amino acid precursors can be somewhat more arduous due to construction of the requisite precursors. A selection of monoalkylidene natural products (1–3) are illustrated that have been the focus of major synthetic efforts.…”

Solid-Phase Total Synthesis of Dehydrotryptophan-Bearing Cyclic Peptides Tunicyclin B, Sclerotide A, CDA3a, and CDA4a using a Protected β-Hydroxytryptophan Building Block

“…Dehydrotryptophan and dehydrotryptophan derivatives exist in a handful of naturally occurring peptides (Figure 1.2). 30 All of these dehydrotryptophan-containing peptides are cyclic and are produced by several different fungal and bacterial strains. In nature, dehydrotryptophan species are produced as a result of direct enzymatic oxidation of L-tryptophan moieties once incorporated into a peptide.…”

“…In contrast, the enzyme tryptophan side chain oxidase produces a mixture of E-and Zdehydrotryptophan species. 30 Only Z-dehydrotryptophan has been found in naturally occurring peptides to date with the cyclic peptide sclerotide B as the sole exception. Sclerotide B discovered by Zhu and coworkers in 2009 was found to contain E-dehydrotryptophan rather than the Z-dehydrotryptophan of sclerotide A (Figure 1.2).…”

Access to Any Site Directed Stable Isotope (2H, 13C, 15N, 17O and 18O) in Genetically Encoded Amino Acids

“…The Vielsmeier-Haack reaction of indole ( 158 ) with dimethyl formamide (165 ) afforded the indole derivative 166 that is reacted with methyl isocyanoacetate ( 45 , Scheme 13) to obtain the isocyano derivative of indole 167 . Mild acid treatment and catalytic asymmetric reduction with D 2 gives the access to prepare tryptophan specifically deuterated in the aliphatic side chain [106,107]. It is also possible to obtain tryptophan via Mannich reaction of indole ( 158 ) [108].…”