Total synthesis of etnangien.
The first total synthesis of the potent RNA-polymerase inhibitor etnangien is described, which establishes unequivocally the relative and absolute configuration of this sensitive macrolide antibiotic. Key features of the expedient and modular synthesis include stereoselective substrate-controlled boron- and tin-mediated aldol couplings to set the characteristic sequences of methyl and hydroxyl bearing stereogenic centers with high degrees of stereoselectivity and yield, an efficient Heck macrocyclization of a conformationally restricted substrate, and a late-stage introduction of the labile side chain. The convergent approach should be amenable to designed analogues.
Li
Pengfei
P
Institut für Organische Chemie, Ruprecht-Karls-Universität Heidelberg, INF 270, D-69120 Heidelberg, Germany.
Li
Jun
J
Arikan
Fatih
F
Ahlbrecht
Wiebke
W
Dieckmann
Michael
M
Menche
Dirk
D
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D018942:Macrolides / Q000138:chemical synthesis*; D011090:Polyenes / Q000138:chemical synthesis*
D000900:Anti-Bacterial Agents; D018942:Macrolides; D011090:Polyenes; C521655:etnangien; D012321:DNA-Directed RNA Polymerases