兰州大学王晓磊团队报道了Miharamycin B及其生物合成前体的不对称从头合成。相关研究成果发表在2022年5月23日出版的《德国应用化学》。

Miharamycins属于肽基核苷类抗生素，具有独特的九碳吡喃基氨基酸核心和罕见的2-氨基嘌呤部分。

该文中，研究人员报道了通过改良的Achmatowicz反应从3-溴呋喃和加纳醛从头全合成Miharamycins B及其生物合成前体。Miharamycins B的从头合成面临许多挑战，包括引入密集的官能团阵列、连续立体中心的立体选择性构建、处理异构体位置的变化以及促进环化形成四氢呋喃环的位置选择性。这种从头合成策略能够高效制备3’-取代糖，能够研究其结构-活性关系和作用模式，并满足受三原霉素天然产物启发开发新型抗生素的日益增长的需求。

附：英文原文

Title: Total Synthesis of Complex Peptidyl Nucleoside Antibiotics: Asymmetric De Novo Syntheses of Miharamycin B and Its Biosynthetic Precursor

Author: Wenjun Huang, Shuai Fan, Jiahui Gao, Shangwen Luo, Shouchu Tang, Jian Liu, Xiaolei Wang

Issue&Volume: 2022-05-23

Abstract: Miharamycins belong to a class of peptidyl nucleoside antibiotics with a unique nine-carbon pyranosyl amino acid core and a rare 2-aminopurine moiety. Herein, we report the de novo total synthesis of miharamycin B and its biosynthetic precursor from 3-bromofuran and Garner’s aldehyde through a modified Achmatowicz reaction. Many challenges were resolved toward the de novo synthesis of miharamycin B, including the introduction of a dense array of functional groups, the stereoselective construction of consecutive stereocenters, dealing with the variability of the anomeric positions, and promoting site-selectivity in the cyclization to form the tetrahydrofuran ring. This de novo synthesis strategy enables efficient preparation of 3’-substituted saccharides, allowing the study of their structure-activity relationships and mode of action, and meets the growing demand for the development of novel antibiotics inspired by miharamycin natural products.

DOI: 10.1002/anie.202204907

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202204907