Ergot alkaloids are known lactation inhibitors and have recently been shown to inhibit prolactin-dependent mammary tumors in rats. Compounds of this type are therefore of interest as potential drugs for the treatment of human breast cancer. Studies on the biosynthesis of ergot alkaloids have progressed to the stage where the choice of compounds which may be invoked as intermediates has narrowed considerably. Further progress requires the synthesis of certain compounds as precursors to the ergoline ring system. It is the objective of this project to synthesize compounds in the ergot alkaloid series which will be tested as: 1) prolactin inhibitors, 2) mammary tumor inhibitors in rats, and/or 3) biosynthetic precursors in the ergot fungus. Approaches to these compounds will involve the development of routes to the clavine alkaloids by semi- and total synthesis. Special emphasis will be given to the design of more potent and long-lasting prolactin inhibitors which will be useful as potential mammary tumor inhibitors.