@article{pittir18236,
          volume = {50},
          number = {13},
           month = {June},
          author = {WH Jung and C Harrison and Y Shin and JH Fournier and R Balachandran and BS Raccor and RP Sikorski and A Vogt and DP Curran and BW Day},
           title = {Total synthesis and biological evaluation of C16 analogs of (-)-dictyostatin},
         journal = {Journal of Medicinal Chemistry},
           pages = {2951 -- 2966},
            year = {2007},
             url = {http://d-scholarship-dev.library.pitt.edu/18236/},
        abstract = {The structure-activity relationship of the crucial C16 region of (-)-dictyostatin was established through total synthesis of analogs followed by detailed biological characterization. A versatile synthetic strategy was used to prepare milligram quantities of 16-normethyldictyostatin, 16-epi-dictyostatin, and the C16-normethyl-C15Z isomer. Along the way, a number of other E/Z isomers and epimers were prepared, and a novel lactone ring contraction to make iso-dictyostatins with 20-membered macrolactones (instead of 22-membered macrolactones) was discovered. The synthesis of 16-normethyl-15,16- dehydrodictyostatin is the first of any dictyostatin by a maximally convergent route in which three main fragments are assembled, coupled in back-to-back steps, and then processed through refunctionalization and macrolactonization. Cell-based and biochemical evaluations showed 16-normethyl-15,16- dehydrodictyostatin and 16-normethyldictyostatin to be the most potent of the new agents, only 2- and 5-fold less active than (-)-dictyostatin itself. This data and that from previously generated dictyostatin analogs are combined to produce a picture of the structure-activity relationships in this series of anticancer agents. {\copyright} 2007 American Chemical Society.}
}