Ring-closing metathesis and photo-fries reaction for the construction of the ansamycin antibiotic kendomycin: development of a protecting group free oxidative endgame.
Two convergent total syntheses of the ansa-polyketide (-)-kendomycin (1) are described. The syntheses benefit from the use of readily available and cheap starting materials. Highly complex diastereoselective Claisen-Ireland rearrangements were used to introduce the (E)-double bond and the C16-Me group. The ring closure of the strained ansa macrocycle was achieved by ring-closing metathesis and a highly efficient combination of macrolactonization and photo-Fries reaction. A protecting group free endgame via an unstable o-quinone is presented. Additionally some unsuccessful synthetic efforts towards the total synthesis of 1 are described.
Magauer
Thomas
T
Institute of Organic Chemistry, University of Vienna, Währingerstrasse 38, 1090 Vienna, Austria.
Martin
Harry J
HJ
Mulzer
Johann
J
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000191:economics / Q000494:pharmacology; D003500:Cyclization; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017828:Rifabutin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000191:economics / Q000494:pharmacology; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; C485395:kendomycin; D017828:Rifabutin