Molecular Design, Chemical Synthesis and Biological Studies of Novel Enediynes Related to Dynemicin A.

Abstract Two novel enediynes 1 and 2 and related molecules containing a (Z)-7-sulfonyl-3-hepten-1,5-diyne functionality and quinoline moiety related to dynemicin A were synthesized from quinoline and 4-methoxyquinoline, respectively. The key synthetic features involve (1) magnesium acetylide addition to the 1-acylsalt of the quinolines (2) a Pd(0)Cu(I) catalyzed coupling reaction of vinyl chloride or aryl iodide with acetylenes (3) conversion of the alcohol to a sulfide, followed by oxidation to a sulfone. These molecules proved to be active against the growth of leukemia, colon, epidermoid and melanoma cancer cell lines.