Cyclopeptide Alkaloids: Stereochemistry and Synthesis of the Precursors of Discarines C and D and Myrianthine A

Abstract

The stereochemistry of discarines C (1) and D (2) and myrianthine A (3), three cyclopeptide alkaloids isolated from Discaria febrifuga, was determined by a combination of NMR studies of 1-3, enantioselective gas chromatography, and comparison of NMR data with those of synthetic tripeptides. For the synthesis of peptides, the nonproteinogenic amino acid 3-phenylserine was also obtained in its four diastereoisomeric forms (l and d threo, obtained by recrystallization of the diastereoisomeric tripeptide, and l and d erythro, obtained by a Mitsunobu reaction with the threo-tripeptides). The general synthetic strategy described in this paper allows the tripeptide to be obtained with the free N-terminal extremity protected or dimethylated. This strategy also allows the synthesis of the corresponding peptide with an imidazolidinone ring.

New bioactive cyclopeptide alkaloids with rare terminal unit from the root bark ofZiziphus cambodiana

“…The 13 C NMR resonances of the chiral carbons observed for 7 were in good agreement with the literature data for frangufoline whose stereochemistry was proven to be all S congurations by the analysis of each amino acid residue in its acid hydrolysate and conrmed by total synthesis. 19,43 The ECD spectrum of 7 exhibited strong negative (239 nm) and positive (287 nm) Cotton effects that also supported the same (5S,8S,9S)-congurations at the 14-membered ring and its negative specic rotation ([a] 39 D À218.5), which led to the conclusion that 7 has the same structure and conguration as the reported frangufoline. In a manner similar to that observed for the other cyclopeptide alkaloids, the 13 C NMR chemical shis at the chiral carbons of 8 are almost identical to those of amaiouine, a structurally related cyclopeptide isolated from Amaioua guianensi that was different from 8 by having a phenylalanine in place of a leucine amino acid in the macrocyclic ring.…”

“…38 Formation of the imidazolidinone ring in cyclopeptide has been implicated from the reaction between the amino acid residue and aldehyde. 34,39 The imidazolidinone ring in compounds 1 and 3 could therefore arise through the condensation of 2 with the respective corresponding carbonyl compounds without an alteration in the amino acid stereocenter.…”

Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia

“…C 86.0 for the L-threo (Fig. 3) (Mostardeiro et al 2013). For the L-erythro series, the signal of the α carbon (C-8) appears at ca.…”

“…C 81.5, whereas for the D-erythro configuration it appears at ca. C 87.0 (Abu-Zarga et al 1995, Caro et al 2012, Dongo et al 1989, Gournelis et al 1997, Medina et al 2016, Mostardeiro et al 2013, Tuenter et al 2016.…”

Approaches to Cyclophane‐Types of Cyclopeptide Alkaloids

“…However, the first total synthesis for most of them are unfinished. For example, the stereochemistry and synthesis of the precursors of discarines C and D and myrianthine A were reported by Morel and co‐workers in 2013 [21] (Scheme 3A). In 2016, the 13‐membered ring cyclopeptide alkaloids of oxyphyllines E, O ‐desmethylnummularine R and O ‐ desmethylnummularine R N ‐oxide were isolated from Ziziphus oxyphylla , and discovered to have antiplasmodial activity [8b] .…”