Syntheses of Monocyclic and Bicyclic Peptides of Tryptathionine and Glycine

Abstract

L‐3a‐Hydroxy‐1.2.3.3a.8.8a‐hexahydropyrrolo[2,3‐b‐]‐indole‐2‐carboxylic acid (Hpi)*, obtained from L‐tryptophan by oxidation with peroxyacetic acid (Savige, 1975), after introduction of the Boc‐residue at N‐1, is coupled with various glycine peptides of S‐trityl‐L‐cysteine to give the Hpi‐peptides 6(a‐f). By treatment with absolute trifluoroacetic acid these peptides are converted by an intramolecular thiolysis to the monocyclic thioethers 7(a‐f). Two of them, 7e and 7f, can be subjected to a second cyclization by the mixed anhydride method thus yielding the bicyclic tryptathionine heptapeptide 8e and octapeptide 8f. In their structures the bicyclic molecules resemble the mushroom phallotoxins and amatoxins, respectively. They show CD spectra closely related to the naturally occurring bicyclic peptides thus indicating conformational similarities. The CD spectra of the other cyclic peptides synthesized are also presented and discussed.

Molecular recognition of organic ammonium ions in solution using synthetic receptors

“…A review of peptide cyclization and cyclopeptides has only recently appeared [731]. Many examples for the synthesis of cyclic and bicyclic peptides can be found in the literature [732–740]. Kubik et al published a comprehensive review about cyclopeptides as macrocyclic hosts [741].…”

Intraannular Savige–Fontana Reaction: One‐Step Conversion of One Class of Monocyclic Peptides into Another Class of Bicyclic Peptides

“…In fact, Zanotti et al. reported on an attempted Savige–Fontana reaction with an N‐acetylated Hpi; no tryptathionine formation was observed, and hence, it was concluded that the N‐acylated Hpi was resistant to acid catalysed ring opening and tryptathionylation 25. 26 In contrast to that finding, here we describe the first synthesis of an intraannular tryptathionine linkage derived from an N‐acylated Hpi moiety incorporated internally within a peptide chain (see below).…”

Bicyclic peptides: types, synthesis and applications

“…To date, several strategies have been used to form synthetic bicyclic peptides. The first strategy was reported to generate a bicyclic tryptathionine heptapeptide in 1978 by Zanotti et al [16]. In this method, the first step of cyclization involved formation of a thioether bond between a cysteine residue and a derivative of Ltryptophan, which was generated by oxidation with peroxyacetic acid.…”