Total syntheses of (+/-)-platencin and (-)-platencin.
The secondary metabolites platensimycin and platencin, isolated from the bacterial strain Streptomyces platensis, represent a novel class of natural products exhibiting unique and potent antibacterial activity. Platencin, though structurally similar to platensimycin, has been found to operate through a slightly different mechanism of action involving the dual inhibition of lipid elongation enzymes FabF and FabH. Both natural products exhibit strong, broad-spectrum, gram-positive antibacterial activity to key antibiotic resistant strains, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant Enterococcus faecium. Described herein are our synthetic efforts toward platencin, culminating in both racemic and asymmetric preparation of the natural product. The syntheses demonstrate the power of the cobalt-catalyzed asymmetric Diels-Alder reaction and the one-pot reductive rearrangement of [3.2.1] bicyclic ketones to [2.2.2] bicyclic olefins.
Nicolaou
K C
KC
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
Tria
G Scott
GS
Edmonds
David J
DJ
Kar
Moumita
M
D000627:Aminophenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002384:Catalysis; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
D000627:Aminophenols; D000900:Anti-Bacterial Agents; D011083:Polycyclic Compounds; C520340:platencin