Second generation synthesis of UCS1025A. synthetic efforts toward total syntheses of CJ-16,264 and Phomopsichalasin.

Abstract

The present work consists primarily of the four projects. The first is methodology for silyl triflate-mediated Dieckmann-like cyclization between esters and imides. The second project is the second generation synthesis of a natural product UCS1025A, which included optimization of the synthesis of the triene precursor of UCS1025A and exploration of its biomimetic Intra-Molecular Diels-Alder (IMDA) cycloaddition. A more efficient way to synthesize the corresponding triene via the MeMgBr-mediated addition of the corresponding vinyl iodide to the enal and optimization of the diastereoselectivity of the final Diels-Alder-cycloaddition to produce UCS1025A are described. The third project, described in Chapter II, is synthetic efforts toward total synthesis of the related natural product CJ-16,264. We have studied the diastereoselective IMDA cycloaddition of the corresponding chiral aldehyde precursor in the presence of MacMillan catalyst followed by BEt3-promoted Reformatski-coupling with iodolactones in the synthesis of various diastereomeric analogs of CJ-16,264. The final project, described in Chapter III, is the synthetic efforts total synthesis of the natural products phomopsichalasin and diaporthichalasin, which we envision to be biosynthesized via a series of two sequential and spontaneous IMDA cycloadditions. Several approaches to the heterocyclic portion of the natural products and their tetraene precursor are described.