The specific objectives of this project are: (a) to synthesize cogeners of synthetic compounds with confirmed activity; (b) to design and synthesize prodrug; (c) to synthesize compounds related to products of natural origin and other related heterocycles; and (d) to synthesize anti-sense nucleic acids. The Contractor shall provide the synthesis effort necessary to advance novel, but flawed, lead anti-AIDS compounds to clinical candidates and for the synthesis of novel compounds based on biochemical/chemical rationale. Often the initially identified lead compounds are flawed because of poor solubility, insufficient stability, and/or narrow spectrum of activity. The "Congener and Prodrug" program will permit the synthesis of clinical anti-AIDS candidate compounds by overcoming these various problems. The quantity of compounds to be synthesized will be dictated by the screening needs.