Total Synthesis of Complex Peptidyl Nucleoside Antibiotics: Asymmetric De Novo Syntheses of Miharamycinâ
B and Its Biosynthetic Precursor.
Angew Chem Int Ed Engl
; 61(31): e202204907, 2022 08 01.
Article
en En
| MEDLINE
| ID: mdl-35606651
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 miharamycinâ
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 miharamycinâ
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antibacterianos
/
Nucleósidos
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2022
Tipo del documento:
Article