| The synthesis of the C14--C26 region of spiro-prorocentrimine (1) was completed in 18 linear steps and 9.3% overall yield. Key transformations include a diastereoselective alkoxy-aldol reaction, an alkyllithium addition to a poly-hydroxylated aldehyde, and a stereoselective lactol reduction. The protecting-group strategy developed for this fragment should allow for a late-stage, selective sulfation of the C19 alcohol.; The development of an iminium-ion Diels-Alder reaction to construct the spirocyclic imine of spiro-prorocentrimine (1) is described. In the presence of Lewis acids, the [4+2] cycloaddition between a cyclic alpha,beta-unsaturated imine dienophile and (E)-1,3-dimethylbutadiene proceeded with good yield and excellent diastereoselection via an endo transition state. The observed spiro-imine contains the desired configuration at the C33 quaternary carbon but the undesired configuration at C9. A revised Diels-Alder strategy, employing a macrocyclic system to control the facial preference of the diene, is proposed.*; *Please refer to dissertation for diagrams. |
