Practical synthesis of prostratin, DPP, and their analogs, adjuvant leads against latent HIV.

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.

Synthesis of the C7-C15 trans decalin portion of the natural antibiotic tetrodecamycin.

[reaction: see text] The tandem oxy-Cope/ene/Claisen rearrangement has been developed in our laboratory as a powerful method for rapid construction of complex Decalin cores. Herein, we describe the use of this method to generate the Decalin core of the natural antibiotic tetrodecamycin (1) bearing six contiguous stereocenters.