The total synthesis of sakyomicin A, an important member of the angucycline class of antibodies and an inhibitor of HIV reverse transcriptase, is the principal goal of the proposed research. The synthetic strategy, outlined in graphical form below, requires the construction of a pre-precursor, a densely functionalized isoquinoline, which when folded into a reactive conformation, will undergo a Bradsher cycloaddition. The product of the cycloaddition is designed to be the ultimate precursor which will then converted to sakyomicin. Our multifaceted studies to be carried out include (i) the introduction of the complex functionality required at C-3 of isoquinoline, (ii) the preparation of simple and complex oxygen functions at C-4, (iii) the Bradsher cycloaddition of C-4 oxygenated isoquinoline and (iv) the further manipulation of cycloaddition products. The MBRS students will work on aspects of part (i).
