Practical synthesis of prostratin, DPP, and their analogs, adjuvant leads against latent HIV
Practical synthesis of prostratin, DPP, and their analogs, adjuvant leads against latent HIV
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DOI：
10.1126/science.1154690
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发表时间：
2008-05-02
期刊：
影响因子：
56.9
通讯作者：
Warrington, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Wender, Paul A.;Kee, Jung-Min;Warrington, Jeffrey M.
虽然抗逆转录病毒疗法在降低艾滋病患者的活性病毒载量方面是有效的，但潜伏病毒储库的持续存在阻碍了病毒的根除。Prostratin和DPP（12-脱氧佛波醇-13-苯乙酸酯）激活潜伏病毒，因此代表了抗病毒治疗的有前途的佐剂。然而，其有限的供应和获取相关结构的挑战阻碍了治疗开发和对临床上优越的上级类似物的搜索。在这里，我们报告了一个实用的合成prostratin和DPP从佛波醇或crotophorbolone，代理商容易从可再生资源，包括生物柴油候选人。这种合成可靠地提供了克量的具有治疗前景的天然产品，迄今为止只能从天然来源获得少量和可变量，并开辟了获得各种新类似物的途径。
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.