Total Synthesis and Structure Elucidation of JBIR‐39: A Linear Hexapeptide Possessing Piperazic Acid and γ‐Hydroxypiperazic Acid Residues |
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| Authors: | Dr. Masahito Yoshida Naoki Sekioka Dr. Miho Izumikawa Dr. Ikuko Kozone Dr. Motoki Takagi Dr. Kazuo Shin‐ya Prof. Dr. Takayuki Doi |
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| Affiliation: | 1. Graduate School of Pharmaceutical Sciences, Tohoku University, 6‐3?Aza‐Aoba, Aramaki, Aoba‐ku, Sendai 980‐8578 (Japan);2. Japan Biological Informatics Consortium, 2‐4‐7?Aomi, Koto‐ku, Tokyo 135‐0064 (Japan);3. Present address: Translational Research Center, Fukushima Medical University, 11‐23?Sakaemachi, Fukushima, 960‐8031 (Japan);4. National Institute of Advanced Industrial Science and Technology (AIST), 2‐4‐7?Aomi, Koto‐ku, Tokyo 135‐0064 (Japan) |
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| 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). |
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| Keywords: | acylation configuration determination natural products peptides total synthesis |
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