Premium
Total Synthesis and Structure Elucidation of JBIR‐39: A Linear Hexapeptide Possessing Piperazic Acid and γ‐Hydroxypiperazic Acid Residues
Author(s) -
Yoshida Masahito,
Sekioka Naoki,
Izumikawa Miho,
Kozone Ikuko,
Takagi Motoki,
Shinya Kazuo,
Doi Takayuki
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201406020
Subject(s) - dipeptide , epimer , chemistry , yield (engineering) , derivative (finance) , stereochemistry , acylation , peptide , catalysis , organic chemistry , biochemistry , materials science , economics , financial economics , metallurgy
The total synthesis and stereochemical structural elucidation of JBIR‐39, containing four nonproteinogenic piperazic acid (Piz) residues, is reported. The synthesis includes Sc(OTf) 3 ‐catalyzed acylation of a Piz(γ‐OTBS) derivative with piperazic acid chloride, providing the desired Piz‐Piz(γ‐OTBS) dipeptide in high yield without epimerization. After assembling two additional Piz moieties and ( S )‐isoleucic acid at the N‐terminus, amidation with the ( R )‐α‐methylserine ester at the C‐terminus, and deprotection afforded the desired (2 R ,8 S )‐hexapeptide, which is the assumed structure of JBIR‐39. Although the spectral data of the (2 R ,8 S )‐hexapeptide was not identical to JBIR‐39, further synthesis of three stereoisomers confirmed the stereochemical structure of JBIR‐39 to be (2 S ,6 S ,8 S ,11 R ,16 S ,21 R ,26 S ,27 S ).