Stereoselective synthesis of c3-c12 dihydropyran portion of antitumor laulimalide using copper-catalyzed oxonium ylide formation-[2,3] shift.
Copper-catalyzed oxonium ylide formation-[2,3] shift of (5S,7R)-5-allyloxy-1-diazo-8-(p-methoxybenzyloxy)-7-methyl-2-octanone (3) proceeded in tetrahydrofuran-dichloromethane (4 : 1) under reflux with an excellent stereoselectivity (97 : 3) to give (2R,6S)-2-allyl-6-[(2R)-3-(p-methoxybenzyloxy)-2-methylpropyl]-3-dihydropyranone (2) as a major isomer in 82% yield. The resultant pyranone (2) was converted to the key intermediate (1) of the Mulzer's laulimalide synthesis and its derivatives (14, 15).
Yakura
Takayuki
T
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Toyama 930-0194, Japan. yakura@ms.toyama-mpu.ac.jp
Muramatsu
Wataru
W
Uenishi
Jun'ichi
J
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001391:Azo Compounds / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry
D000970:Antineoplastic Agents; D001391:Azo Compounds; D018942:Macrolides; D043823:Taxoids; C117305:laulimalide; D003300:Copper