This talk will discuss the total syntheses of complex Galbulimima alkaloids himbacine and himgaline and a case history for the discovery of SCH 530348, a thrombin receptor antagonist (TRA) that is currently undergoing Phase-III clinical trials for myocardial infarction. The lead for the TRA program was a synthetic analog of himbacine. After achieving a practical synthesis of himbacine analogs, extensive lead optimization went through several years of efforts and synthesis of thousands of analogs. The final development candidate SCH 530348 showed potent antiplatelet effect in a number of functional assays and in a monkey ex-vivo model. The compound was subsequently progressed to clinical studies