A chemoenzymatic and fully stereocontrolled total synthesis of the antibacterial natural product (-)-platencin.
The natural product (-)-platencin is a potent antibacterial agent that exerts its effects through a novel mode of action. As such, it is an important lead in the development of next-generation antibacterials that are urgently needed because of the rapidly developing resistance to current therapies. The work reported here concerns the development of a convergent and chemoenzymatic total synthesis of (-)-platencin by methods that should provide access to a range of biologically relevant analogues. The key step involves a thermally promoted and facially selective intramolecular Diels-Alder (IMDA) cycloaddition reaction to give an adduct that embodies the tricarbocyclic core of (-)-platencin. This adduct was elaborated over thirteen steps to the natural product. The substrate for the IMDA reaction was prepared by Stille cross-coupling of a Z-configured alkenylstannane with an iodinated diene obtained in an enantiomerically pure form through the whole-cell biotransformation of iodobenzene.
Research School of Chemistry, Australian National University, Canberra, ACT 2601 (Australia).
Ee Ling
EL
Chang
Brett D
BD
Schwartz
Alistair G
AG
Draffan
Martin G
MG
Banwell
Anthony C
AC
Willis
D000627:Aminophenols / Q000138:chemical synthesis* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D061565:Cycloaddition Reaction; D008968:Molecular Conformation; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000627:Aminophenols; D000900:Anti-Bacterial Agents; D011083:Polycyclic Compounds; C520340:platencin
chirality; cross-coupling; cycloaddition; natural products; total synthesis