Total Synthesis of a Macrocyclic Lactone Antibiotic A26771B and Its Isomers Using Carbohydrates

Publisher Website
Google Scholar
Abstract
Total synthesis and antibacterial activities of a macrocyclic lactone antibiotic A26771B (1) and all its isomers (2, 3, and 4) are discussed. The starting 8,9,10,12-tetra-O-benzyl-2,3,4,5,11-pentadeoxy-aldehydo-d-xylo-(E)-6-dcdecenose derived from d-glucose reacted with racemic Wittig reagent, (3-hydroxybutyl)triphenylphosphonium iodide to give 1,3,4,5-tetra-O-benzyl-2,8,9,10,11,14,16-heptadeoxy-Dl-glycero-l-xylo-hexadeca-6,12-dienitol, which was in turn converted into methyl 15-O-acetyl-6,7,8,9,10,11,12,13,14,16 -decadeoxy-4,5-O-isopropylidene-Dl-glycero-l-threo-(E)-2-hexadecenonate (13) through effective oxidation and β-elimination. Saponification followed by Yamaguchi’s lactonization of 13 afforded two diastereomeric 16-membered-ring lactones which were converted into (5S, 15R)-A26771B (1) and its (5S, 15S-diastereomer (2) by successive deacetonation, selective succinylation and oxidation. The other starting 2,3,4,6-tetra-O-benzyl-5-deoxy-aldehydo-d-lyxo-hexose, which was prepared from 2-deoxy-d-glucose, reacted with a Wittig reagent to give 8,9,10,12-tetra-O-benzyl-2,3,4,5,11-pentadeoxy-aldehydo-d-lyxo-6-dodecenose (20) followed by hydrol ysis. Similar reaction sequence from 20 with the aforesaid series for 1 and 2 afforded the (5R, 15R)-isomer (3) and (5R, 15S)-isomer (4).