title: Total synthesis and structure elucidation of JBIR-39: a linear hexapeptide possessing piperazic acid and γ-hydroxypiperazic acid residues.
abstract: 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 (2R,8S)-hexapeptide, which is the assumed structure of JBIR-39. Although the spectral data of the (2R,8S)-hexapeptide was not identical to JBIR-39, further synthesis of three stereoisomers confirmed the stereochemical structure of JBIR-39 to be (2S,6S,8S,11R,16S,21R,26S,27S).
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8578 (Japan).
authors.forename: Masahito
authors.initials: M
authors.lastname: Yoshida
authors.forename: Naoki
authors.initials: N
authors.lastname: Sekioka
authors.forename: Miho
authors.initials: M
authors.lastname: Izumikawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kozone
authors.forename: Motoki
authors.initials: M
authors.lastname: Takagi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-Ya
authors.forename: Takayuki
authors.initials: T
authors.lastname: Doi
mesh_terms: D000215:Acylation; D001688:Biological Products; D015394:Molecular Structure; D011724:Pyridazines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D011724:Pyridazines; C014756:piperazic acid
keywords: acylation; configuration determination; natural products; peptides; total synthesis