Total Syntheses of Lactonamycin and Lactonamycin Z with Late‐Stage A‐Ring Formation and Glycosylation

Abstract

Die hoch oxygenierten Polyketid‐Antibiotika Lactonamycin und Lactonamycin Z wurden synthetisiert. Das BCDEF‐Ringsystem wurde durch eine Cycloaddition und eine Palladium‐katalysierte Cyclisierung aufgebaut; eine Bischler‐Napieralski‐Cyclisierung wurde zum Aufbau des A‐Rings genutzt. Die Glycosylierung des Aglycons mit dem richtigen Zucker ergab Lactonamycin und Lactonamycin Z.

Divergent Strategy in Natural Product Total Synthesis

“…Structurally, the ergot alkaloids feature a unique tetracyclic ergoline skeleton containing several chiral centers of various configurations. In 2017, Jia and coworkers reported an efficient and divergent total synthesis tactic to eight ergot alkaloids, which are festuclavine (192), pyroclavine (193), costaclavine (197), epi-costaclavine (198), pibocin A (195), 9-deacetoxyfumigaclavine C (194), fumigaclavine G (196), and dihydrosetoclavine (190) (Scheme 18). 57 The key step of this synthesis is the use of a palladium-catalyzed intramolecular Larock annulation to assemble 3,4-fused indoles that was developed by them in 2013. carbamate 187 with LiAlH 4 and Raney Ni gave festuclavine (192) and pyroclavine (193) with a ratio of 5:3.…”

“…In addition, intermediate 188 could be transformed to compound 189 over four steps. Hydrogenation of 189 with Crabtree's catalyst provided costaclavine (197) and epicostaclavin (198).…”

“…Similarly, (+)-secohyperforin (1571) was also readily synthesized from 1568 in four steps. 197 The synthesis commenced with the known phenol 1586, which was transformed to anhydride 1587 in seven steps. Cycloaddition of the diene generated from 1587 with quinone 1588 afforded 1589.…”

Total Synthesis of Tetarimycin A, (±)-Naphthacemycin A9, and (±)-Fasamycin A: Structure–Activity Relationship Studies against Drug-Resistant Bacteria

“…and concentrated to give the crude residue, which was recrystallized with EtOAc and n-hexane to afford benzaldehyde 21 (8.5 g, 93% yield) as a white solid: 14 mp 70−71 °C; 1 H NMR (CDCl 3 , 400 MHz) δ 3.90 (s, 6H), 5.05 (s, 2H), 6.44 (s, 1H), 6.76 (s, 1H), 10.46 (s, 1H); 13 C NMR (CDCl 3 , 100 MHz) δ 44.8, 55. 6, 56.0, 97.6, 107.5, 115.9, 142.3, 165.0, 165.3, 189.9. 7-Hydroxy-5-methoxyisobenzofuran-1(3H)-one (22). To a stirred solution of 21 (9.7 g, 45.2 mmol) in dry DCM (180 mL) at 0 °C was added BCl 3 (1 M in DCM, 60 mL, 60 mmol) under N 2 .…”

Isoindolinone Synthesis: Selective Dioxane-Mediated Aerobic Oxidation of Isoindolines

“…41 A recent Bischler−Napieralski-type cyclization 42 allowed the late stage construction of an isoindolinone in the total synthesis of lactonamycin. 43 Recently, a method for 1°and 2°amine oxidation prepared unsubstituted isoindolinone in good yield. 44 However, the oxidation of N-substituted isoindolines, 1, as demonstrated in this note, is an underexplored approach to isoindolinones, 2.…”