Development of syn-1,3-diol methodologies and their applications to biologically active molecules

This thesis describes the development of syn-1,3-diol methodologies and their applications in the synthesis of compactin lactone and the synthetic approach towards griseoviridin.; In part 1, the development of syn-1,3-diol methodologies is presented. The first methodology involves the nitro aldol reaction of α-alkoxy aldehydes with nitro compounds to build β-alkoxy ketones. Chelation controlled reduction of the β-alkoxy ketones with LiAlH₄/LiI provided the syn-1,3-diols in excellent selectivity. The selectivity was improved by enhancing the metal chelation between the ketone oxygen and the β-ether oxygenor by reducing the competing chelation of the β ′-ether oxygen with the ketone oxygen. In our second syn-1,3-diol methodology, enzyme-catalyzed enantioselective acylation of a racemic alcohol and ring-closing olefin metathesis resulted in the α,β-unsaturated-δ-lactone were utilized as the key steps. Both methodologies were applied in the synthesis of a biologically active molecule, compactin lactone.; Part 2 describes our synthetic approach towards griseoviridin. The oxazole diene fragment was synthesized starting from the syn -1,3-diol fragment obtained from part 1. The diene moiety was constructed by Pd-catalyzed allylic azidation of bis-allyl ester. The skeleton of the nine-membered ring lactone was constructed by an unprecedented intramolecular nucleophilic substitution reaction. The double bond moiety was introduced by an improved Pummerer reaction.