Total Synthesis of Complex Peptidyl Nucleoside Antibiotics: Asymmetric De Novo Syntheses of Miharamycin B and Its Biosynthetic Precursor. (20th June 2022)

• Record Type: Journal Article
• Authors: Huang, Wenjun; Fan, Shuai; Gao, Jiahui; Luo, Shangwen; Tang, Shouchu; Liu, Jian; Wang, Xiaolei
• Is Part Of: Angewandte Chemie. Volume 134:Number 31(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-20
• Subjects: Biosynthetic Precursors -- Carbohydrates -- Natural Products -- Nucleoside Antibiotics -- Total Synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202204907
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Simple building blocks were used for the total synthesis of miharamycin B and its biosynthetic precursor. The key step in the strategy was the de novo construction of the pyranose moiety through Achmatowicz rearrangement. The purine ring was introduced by palladium‐catalyzed N‐glycosylation.