The long range goal of this work is the development of efficient syntheses for the naturally occurring antibiotics tirandamycin/streptolydigin and BU2313A&B and the marine toxin aplysiatoxin. An integral part of this effort will be to use these synthetic procedures for the construction of non-natural analogs of these biologically active compounds. For the antibiotics tirandamycin/streptolydigin, initial specific target analogs will be those in which the tetramic acid portion is varied. The marine toxin, aplysiatoxin, is an activity anti-Leukemic agent and has been shown to a co-carcinogen. After a route to this molecule is developed, selected structural changes will be explored. Initial changes will involve modification of the side-chains appended to the nuclear spiroketal system. The analog work will be directed to help define the anti-neoplastic activity of this molecule. The development of tirandamycin/streptolydigin synthetic strategy is well advanced and quantities of the top portion of these antibiotics should soon be available. Preliminary work on the BU2313A&B and the aplysiatoxin syntheses has defined viable approaches to each system, and these will be pursued.