Chemical modification of a highly functionalized taxane. The consequences of an absent bridgehead double bond on oxetane D-ring construction.
An oxetane D-ring has been fused to the framework of the highly functionalized taxane 2. The synthetic route is based on a trimethylsilyl triflate-promoted epoxide-opening step, followed by stereocontrolled, regioreversed oxirane formation and reductive transposition of this intermediate with bis(cyclopentadienyl)titanium(III) chloride. This last key step provides for the convenient implementation of additional hydroxyl groups ultimately conducive to intramolecular S(N)2 reaction. Tangential features of the route outlined herein include specific rearrangement reactions and a retro-aldol cleavage of ring A.
Paquette
Leo A
LA
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA. paquette.1@osu.edu
Lo
Ho Yin
HY
D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D007202:Indicators and Reagents; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D017239:Paclitaxel / Q000737:chemistry*; D013329:Structure-Activity Relationship; D043823:Taxoids; D013816:Thermodynamics
D001952:Bridged-Ring Compounds; D007202:Indicators and Reagents; D043823:Taxoids; C080625:taxane; D017239:Paclitaxel