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The first chemical synthesis of the promising antiangiogenic agent cortistatin A has been achieved by Phil S. Baran and coworkers at Scripps Research Institute (J. Am. Chem. Soc., DOI: 10.1021/ja8023466). Antiangiogenic agents such as cortistatin A, which was discovered in a marine sponge in 2006, inhibit the growth of blood vessels. The mechanism of action of this selective, nontoxic, and potent antiangiogenic molecule remains undetermined, but it seems to be different from those of other known antiangiogenic agents. Drug companies and researchers would like to obtain cortistatin A and other members of the cortistatin family for biological and possibly. clinical studies for conditions such as macular degeneration and cancer. But the compounds have been hard to get, and various organic chemistry groups have been trying to synthesize cortistatin A to improve its availability. Baran and coworkers have now succeeded by making the compound's core structure from prednisone, a readily available commercial immunosuppressant, and then adding isoquinoline. The relatively short, 3%-yield procedure is readily modifiable and should thus allow for the synthesis of useful quantities of cortistatin A, other cortistatins, and related analogs.
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