[Total synthesis of EPO D -- Protarga]
>>Bioorg Chem. 2005 Apr;33(2):116-33. Epub 2004 Dec 15.
Total synthesis of 12,13-desoxyepothilone B (Epothilone D).
Broadrup RL, Sundar HM, Swindell CS.
Protarga, Inc., 2200 Renaissance Blvd., Suite 450, King of Prussia, PA 19406, USA; Department of Chemistry, Bryn Mawr College, Bryn Mawr, PA 19010, USA.
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).<<
Not being a chemist, I have no idea if this is more efficient than Kosan's modified bugs. But my guess -- from my lay interpretation of the nomenclature in this abstract that seems to imply roughly 30 steps -- is that the bacteria do the job much more easily. These guys are just showing it can be done without 'em, not that it's a great idea to do so, IMO.
Cheers, Tuck |
