Highly selective asymmetric acetate aldol reactions and their application to the total synthesis of dermostatin A

The first part of this thesis describes studies of new asymmetric acetate aldol methods. A highly diastereoselective acetate aldol reaction that uses the L-tert-leucine-derived thiazolidinethione auxiliary has been developed. The reaction proceeds in excellent yields and with high diastereoselectivities (diastereomeric ratios range from 9.5:1 to >100:1). Because D-tert -leucine is prohibitively expensive, a new N-acetyl thiazolidinethione reagent which has the same sense of chirality as the D- tert-leucine derived reagent from the inexpensive amino acid, L-cysteine has been synthesized. This compound is very similar in its reactivity to the tert-leucine-derived reagent and also provides high yields and diastereoselectivities. Double diastereoselection in the addition of these reagents to chiral aldehydes which model the types of substrates that are commonly encountered in polyacetate synthesis has also been studied. It was found that asymmetric induction from the chiral auxiliary predominates over that of the aldehyde, thereby further broadening the scope of this useful asymmetric acetate aldol reaction method.; The second part of this thesis describes a full account of studies which culminated in the total synthesis of the polyene macrolide dermostatin A. The research was focused on the development of novel methods for the assembly of skipped polyol chains. The fully protected polyol was rapidly synthesized, starting a double asymmetric acetate reaction using a reagent developed in our laboratory. The use of a remote asymmetric induction strategy for fragment union proceeds with high diastereoselectivity. Also notable is the use of an olefin cross-metathesis strategy on a complex substrate to install the polyene of dermostatin A.