- Amphidinolide B: Total synthesis, structural investigation, and biological evaluation
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The total syntheses of amphidinolide B1 and the proposed structure of amphidinolide B2 have been accomplished. Key aspects of this work include the development of a practical, non-transition-metal-mediated method for the construction of the C13-C15 diene, the identification of α-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy, and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B2 and diastereomers thereof display potent antitumor activities with IC50 values ranging from 3.3 to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B2 is over 12-fold more potent than the C8,9-epimer and C18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.
- Lu, Liang,Zhang, Wei,Nam, Sangkil,Horne, David A.,Jove, Richard,Carter, Rich G.
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p. 2213 - 2247
(2013/05/09)
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- REGIOSELECTIVITY IN INTRAMOLECULAR ADDITION OF ALLYLSILANES TO CONJUGAT DIENONES
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The intramolecular addition of allylsilanes to conjugated dienones shows a divergence of regioselectivity as a function of reagent and substrate structure.The creation of 5-5, 6-5, 5-7, and 6-7 bicyclic ring systems is reported.
- Majetich,G,Hull,K,Defauw,J,Desmond,R
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p. 2747 - 2750
(2007/10/02)
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- AN EFFECT SILICON SUBSTITUTION REMOTE FROM REACTIVE SITE
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The source of a rate retardation of the trimethylsilyl substituent in an alkylation reaction is probed.
- Trost, Barry M.,Curran, Dennis P.
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p. 5023 - 5026
(2007/10/02)
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