Wender Paul A, Kee Jung-Min, Warrington Jeffrey M
Department of Chemistry, Stanford University, 337 Campus Drive, Stanford, CA 94305, USA.
Science. 2008 May 2;320(5876):649-52. doi: 10.1126/science.1154690.
Although antiretroviral therapies have been effective in decreasing active viral loads in AIDS patients, the persistence of latent viral reservoirs prevents eradication of the virus. Prostratin and DPP (12-deoxyphorbol-13-phenylacetate) activate the latent virus and thus represent promising adjuvants for antiviral therapy. Their limited supply and the challenges of accessing related structures have, however, impeded therapeutic development and the search for clinically superior analogs. Here we report a practical synthesis of prostratin and DPP starting from phorbol or crotophorbolone, agents readily available from renewable sources, including a biodiesel candidate. This synthesis reliably supplies gram quantities of the therapeutically promising natural products, hitherto available only in low and variable amounts from natural sources, and opens access to a variety of new analogs.
尽管抗逆转录病毒疗法在降低艾滋病患者的活跃病毒载量方面已取得成效，但潜伏病毒库的持续存在阻碍了病毒的根除。原锥虫素和DPP（12-脱氧佛波醇-13-苯乙酸酯）可激活潜伏病毒，因此是抗病毒治疗中颇具前景的佐剂。然而，它们的供应有限以及获取相关结构面临的挑战，阻碍了治疗开发以及寻找临床上更优的类似物。在此，我们报道了一种从佛波醇或巴豆佛波醇酮出发实用的原锥虫素和DPP合成方法，这些起始原料可从包括生物柴油候选物在内的可再生资源中轻松获得。这种合成方法可靠地提供了克级量的具有治疗前景的天然产物，这些天然产物迄今仅能从天然来源以少量且产量不稳定的形式获得，并且为获取各种新的类似物开辟了道路。
