Applications of enantioselective halolactonization reactions, synthesis of photocaged compounds for identifying neurons based on function, and progress towards the total synthesis of alstoscholarisine E
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Recently the Martin group developed a bifunctional organic catalyst that promotes highly efficient enantioselective halolactonization reactions for olefinic acids. Using the BINOL-amidine catalyst we invented, our group was able to perform halolactonization reactions on a broad array of substrates. Herein we describe the synthetic utility of this method through a concise synthesis of (+)-disparlure, along with the preparation of F ring synthons for the natural product kibdelone C. As part of a separate project, in collaboration with the Zemelman research group, we are working to design a system for identifying behaviorally relevant assemblies of neurons in awake animals. This novel technique identifies active neurons and tags them using fluorescent proteins that are expressed upon irradiation of the neuron with visible light. This system hinges on the preparation on light sensitive derivatives of a variety of repressor protein ligands using “cages” or “photocages.” Toward this end, we prepared photocaged derivatives of anhydrotetracycline and vanillic acid. Finally, we disclose our progress towards the total synthesis of alstoscholarisine E, a natural product isolated in 2014 that was found to be a strong promoter of adult neuronal stem cell proliferation. We envisioned a convergent synthesis where skatole and a hetero-Diels-Alder product could be joined through a metal catalyzed coupling to form the tetracyclic core of the molecule, which could then be easily transformed to alstoscholarisine E through an olefin reduction followed by a reductive cyclization. Accessing our desired hetero-Diels-Alder product quickly was paramount to the effectiveness of this route, and thus, we developed a method to access hetero-Diels-Alder precursors in one step starting from readily available hexahydrotriazines.