1403355-65-6Relevant articles and documents
Synthetic studies towards the core tricyclic ring system of pradimicin A
Zilke, Laura,Hall, Dennis G.
, p. 4153 - 4163 (2012)
Pradimicins are structurally intriguing natural products that possess potent biological activity as antifungal and antiviral agents through a unique mode of action as carbohydrate binding agents. A preliminary synthetic approach towards pradimicin A has focused on a model study of the core tricyclic ring system. The route features an alkoxyallylboration/cycloisomerization/Diels-Alder cycloaddition sequence as the key steps. The alkoxyallylboration was critical for differentiating the hydroxy groups in the central cyclohexadienediol unit of pradimycins, which will ensure a regiocontrolled glycosylation. For the cycloisomerization reaction, various substrates and conditions were tested for a ring-closing enyne metathesis reaction. With enyne substrate 23, dimerization-prone bicyclic diene 24 was isolated as the major product under the conditions of both ruthenium-catalyzed metathesis and palladium-catalyzed cycloisomerization. In the end, the optimal route found for the synthesis of the model functionalized tricyclic ring system 31 features a one-pot sequential palladium-catalyzed cycloisomerization, Diels-Alder reaction, and oxidative aromatization. A model study towards the synthesis of the C-D-E tricyclic core of the carbohydrate binding agent, pradimicin A, is described. Alkoxyallylboration provided the differentially protected diol unit of the central ring. Optimization of a key enyne cycloisomerization reaction led to the synthesis of the tricycle by a one-pot Pd-catalyzed cycloisomerization/Diels- Alder cycloaddition/aromatization.
