Wilson Rebecca M, Danishefsky Samuel J
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
J Org Chem. 2006 Oct 27;71(22):8329-51. doi: 10.1021/jo0610053.
Natural products have been a rich source of agents of value in medicine. They have also inspired, at various levels, the fashioning of nonnatural agents of pharmaceutical import. Hitherto, these nonnatural derivatives have been primarily synthesized by manipulating the natural product. As a consequence of major innovations in the subscience of synthetic methodology, the capacity of synthesis to deal with molecules of considerable complexity has increased dramatically. In this paper, we show by example some total syntheses which draw from strategy-enabling advances in methodology. Moreover, we show how these capabilities can be used to discover and develop new agents of potential pharmaceutical value without recourse to the natural product itself.
天然产物一直是医学中有价值药物的丰富来源。它们还在各个层面启发了具有药学意义的非天然药物的创制。迄今为止，这些非天然衍生物主要是通过对天然产物进行改造来合成的。由于合成方法学这一细分学科的重大创新，合成处理相当复杂分子的能力大幅提高。在本文中，我们通过实例展示了一些全合成，这些全合成借鉴了方法学中有助于实现策略的进展。此外，我们还展示了如何利用这些能力来发现和开发具有潜在药学价值的新药物，而无需借助天然产物本身。
