Renieramycin-type bis-1,2,3,4-tetrahydroisoquinoline marine natural products

Marine organisms are a valuable source of lead compounds for drug development, and basic research. This field has been active for nearly half a century. However, because of their unique structures and poor chemical stability, it is difficult to achieve a sustainable, large-scale supply of marine natural products and thus, their use in drug development is rare. Renieramycin was first reported in 1982 by Fricke and Faulkner as a trace secondary metabolite from the blue sponge Reniera sp. Dimeric 1,2,3,4-tetrahydroisoquinoline derivatives, such as renieramycins, have attracted attention as novel anticancer agents. Therefore, challenges related to chemical stability and transformations, as well as development of total syntheses were overcome. Several excellent reviews on renieramycin marine natural products have been published. Research in the renieramycin family has been developed based on the results of various previous studies on saframycin, an antibiotic discovered from the Actinomycete Streptomyces lavendulae No. 314. In this review, we will introduce from a new perspective the results of ongoing efforts in the medicinal chemistry. We will explore the discovery, chemical transformation, total synthesis, and structure-activity relationships of renieramycin marine natural products, highlighting unexpected findings that emerged during the research process.¹.