Total synthesis of platensimycin and related natural products.
Platensimycin is the flagship member of a new and growing class of antibiotics with promising antibacterial properties against drug-resistant bacteria. The total syntheses of platensimycin and its congeners, platensimycins B(1) and B(3), platensic acid, methyl platensinoate, platensimide A, homoplatensimide A, and homoplatensimide A methyl ester, are described. The convergent strategy developed toward these target molecules involved construction of their cage-like core followed by attachment of the various side chains through amide bond formation. In addition to a racemic synthesis, two asymmetric routes to the core structure are described: one exploiting a rhodium-catalyzed asymmetric cycloisomerization, and another employing a hypervalent iodine-mediated de-aromatizing cyclization of an enantiopure substrate. The final two bonds of the core structure were forged through a samarium diiodide-mediated ketyl radical cyclization and an acid-catalyzed etherification. The rhodium-catalyzed asymmetric reaction involving a terminal acetylene was developed as a general method for the asymmetric cycloisomerization of terminal enynes.
Nicolaou
K C
KC
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. kcn@scripps.edu
Li
Ang
A
Edmonds
David J
DJ
Tria
G Scott
GS
Ellery
Shelby P
SP
D000218:Adamantane / Q000138:chemical synthesis* / Q000737:chemistry; D000447:Aldehydes / Q000138:chemical synthesis; D062365:Aminobenzoates / Q000138:chemical synthesis* / Q000737:chemistry; D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D007536:Isomerism; D012238:Rhodium / Q000737:chemistry
D000447:Aldehydes; D062365:Aminobenzoates; D000813:Anilides; D000900:Anti-Bacterial Agents; D001688:Biological Products; D012238:Rhodium; D000218:Adamantane; C510909:platensimycin