Asymmetric synthesis of triepoxyzerumbol

The achiral sesquiterpene zerumbone 1, which is readily available from wild ginger, has a unique functionality and reactivity making it a convenient starting material for its conversion into useful compounds, such as paclitaxel. Optically active triepoxyzerumbol (−)-3 and its acetate (+)-4 were synthesized by lipase-catalyzed enantioselective transesterification of racemic 3. Under optimized conditions, a lipase from Alcaligenes sp. (Meito QL) catalyzed the reaction of racemic 3 with isopropenyl acetate in THF at 35 °C to afford (1S)-3 and (1R)-4 with an E-value of 79. The absolute configuration of (1R)-4 was determined by single crystal X-ray diffraction of its ester with a chlorine atom using the anomalous dispersion effect.

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(1R,2R,3S,6S,7S,10S,11R)-1-Acetoxy-2,3-6,7-10,11-triepoxy-2,6,9,9-tetramethylcycloundecaneC17H26O5Ee = 96% [capillary GC with chiral column (CPCD)][α]D23.5=+50.6 (c 1.00, CHCl3)Absolute configuration: (1R,2R,3S,6S,7S,10S,11R)

(1R,2S,3S,6S,7S,10S,11S)-2,3-6,7-10,11-Triepoxy-2,6,9,9-tetramethylcycloundecan-l-olC15H24O4Ee = 96% [capillary GC with chiral column (CPCD)][α]D23.5=+111.1 (c 1.00, CHCl3)Absolute configuration: (1R,2S,3S,6S,7S,10S,11S)

(1S,2R,3R,6R,7R,10R,11R)-2,3-6,7-10,11-Triepoxy-2,6,9,9-tetramethylcycloundecan-l-olC15H24O4Ee = 45% [capillary GC with chiral column (CPCD)][α]D23.5=−58.8 (c 1.00, CHCl3)Absolute configuration: (1S,2R,3R,6R,7R,10R,11R)