Yoshida Masahito, Sekioka Naoki, Izumikawa Miho, Kozone Ikuko, Takagi Motoki, Shin-Ya Kazuo, Doi Takayuki
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8578 (Japan).
Chemistry. 2015 Feb 9;21(7):3031-41. doi: 10.1002/chem.201406020. Epub 2014 Dec 18.
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).
报道了含有四个非蛋白质ogenic哌嗪酸（Piz）残基的JBIR - 39的全合成及其立体化学结构解析。合成过程包括用三氟甲磺酸钪（Sc(OTf)3）催化Piz(γ - OTBS)衍生物与哌嗪酸氯进行酰化反应，以高收率得到所需的Piz - Piz(γ - OTBS)二肽且无差向异构化。在N端组装另外两个Piz部分和（S）-异亮氨酸，在C端与（R）-α-甲基丝氨酸酯进行酰胺化反应，然后脱保护得到所需的（2R，8S）-六肽，其为JBIR - 39的假定结构。尽管（2R，8S）-六肽的光谱数据与JBIR - 39不完全相同，但进一步合成三种立体异构体证实了JBIR - 39的立体化学结构为（2S，6S，8S，11R，16S，21R，26S，27S）。
