Total synthesis, stereochemical assignment, and biological evaluation of opantimycin A and analogues thereof.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-10-18 DOI:10.1039/d4ob01475h

Yoshinosuke Usuki, Ryota Abe, Kazuki Nishiguchi, Tetsuya Satoh, Harumi Aono, Toshihiko Nogawa, Yushi Futamura, Hiroyuki Osada, Izumi Yoshida, Kazuhiro Fujita, Takashi Mishima, Ken-Ichi Fujita

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Abstract

Opantimycin A, a rare antimycin-class antibiotic without the macrolide core, was isolated from Streptomyces sp. RK88-1355 in 2017. In this study, we explored the total synthesis and stereochemical assignment of opantimycin A. The synthesis of all potential diastereomers has been accomplished via traceless Staudinger ligation. A comparison of the spectroscopic data of the synthesized compounds with that reported for the natural product confirmed that the absolute configuration of the natural product was (14S,17R,21R). Two analogous compounds were prepared, where the Dhb ((Z)-dehydrobutyrine) moiety was replaced with Dha (dehydroalanine) or ΔVal moieties, respectively. The inhibitory activities of these synthetic compounds against the production of the anti-inflammatory cytokine IL-6 were evaluated, and two potential candidates for further development as anti-inflammatory agents were identified.

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欧潘霉素 A 及其类似物的全合成、立体化学分配和生物学评价。

2017 年，从链霉菌 RK88-1355 中分离出一种罕见的无大环内酯核心的抗霉素类抗生素--奥潘霉素 A。在这项研究中，我们探索了奥潘霉素 A 的全合成和立体化学分配。所有潜在非对映异构体的合成都是通过无踪施陶丁格连接完成的。将合成化合物的光谱数据与天然产物的光谱数据进行比较，证实天然产物的绝对构型为 (14S,17R,21R)。我们还制备了两种类似化合物，分别用 Dha（脱氢丙氨酸）或 ΔVal 取代了 Dhb（(Z)-脱氢丁碱）分子。评估了这些合成化合物对抗炎性细胞因子 IL-6 生成的抑制活性，并确定了两种可进一步开发为抗炎剂的潜在候选化合物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464