| A synthetic approach to cochleamycin A based on a biomimetic transannular Diels-Alder reaction is described. The synthesis of a macrocyclic lactone tetraene was accomplished in 22 steps and 4% overall yield. Key steps in the synthesis include a Suzuki cross-coupling reaction, a π-allylpalladium macrocyclization, and a selenoxide elimination. Upon thermolysis, this intermediate irreversibly isomerized to a macrocyclic 2H-pyran, which did not undergo a transannular Diels-Alder reaction.*; A modified ester-derived tetraene was synthesized in 20 steps and 6% overall yield. Thermolysis of this intermediate induced a highly selective Diels-Alder reaction to generate a single diastereomeric product. Although this product possessed the undesired C4–C5 alkylidene geometry, it contained the correct A-B-C ring system of 1, and represents the complete carbon skeleton of the cochleamycins. However, elaboration of this Diels-Alder adduct to cochleamycin A has not been achieved to date.; *Please refer to dissertation for diagrams. |
