Total synthesis of 12,13-desoxyepothilone B (Epothilone D).
A highly convergent total synthesis of 12,13-desoxyepothilone B (4, Epothilone D) is described involving the coupling of vinyl iodide (5) and olefin (6). Key steps in the synthesis are the introduction of chirality at C15 via highly enantioselective lipase-mediated enzymatic resolution, diastereoselective alkylation at C8, highly diastereoselective Evans aldol reaction to establish C6-C7, and Mukaiyama aldol reaction to introduce chiral center C3. Palladium catalyzed Suzuki coupling of (5) and (6) provided the methyl ester (27), which was converted to 12,13-desoxyepothilone B (4).
Broadrup
Robert L
RL
Protarga, Inc., King of Prussia, PA 19406, USA. organicrob@comcast.net
Sundar
Hema M
HM
Swindell
Charles S
CS
D000475:Alkenes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002384:Catalysis; D034261:Epothilones / Q000138:chemical synthesis*; D007454:Iodides; D010165:Palladium; D014753:Vinyl Compounds
D000475:Alkenes; D000970:Antineoplastic Agents; D034261:Epothilones; D007454:Iodides; D014753:Vinyl Compounds; D010165:Palladium; C114026:desoxyepothilone B