An efficient and stereoselective synthesis of xerulin via Pd-catalyzed cross coupling and lactonization featuring (E)-lodobromoethylene as a novel two-carbon synthon.
[structure: see text] Xerulin, an inhibitor of cholesterol biosynthesis, has been synthesized from commercially available (E)-1-bromopropene, acetylene, and propynoic acid in five steps (longest linear sequence) in 30% overall yield and >96% stereoselectivity. The preparation of (E)-iodobromoethylene and its use in the Pd-catalyzed cross coupling are two of the novel aspects of the synthesis reported herein.
Negishi
E
E
Herbert C. Brown Laboratories, Purdue University, West Lafayette, Indiana 47907, USA. negishi@purdue.edu
Alimardanov
A
A
Xu
C
C
D000924:Anticholesteremic Agents / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism
D000924:Anticholesteremic Agents; D007783:Lactones; C066799:xerulin