Control of stem cell fate is a central goal of regenerative medicine. Hematopoietic

stem cells (HSCs) are in high demand because they are routinely used in bone marrow

transplants. This has led to a shortage of clinically viable HSCs and there are no FDA

approved methods for the growth and maintenance of these cells ex vivo. The natural

product eupalinilide E (7) promotes the ex vivo self-renewal (expansion) of HSCs with a

983-fold increase in growth after 14 days. The mode of action of eupalinilide E (7) remains unknown and appears to be independent of other known mechanism for HSC expansion. A synthetic route that can allow access to gram-scale quantities of eupalinilide E (7) has been developed.

There remains a constant need for novel antibiotics to combat the ever growing

problem of antibiotic resistant infections. Thiopeptides are a well-studied family of natural

products with potent antibiotic activity against several contemporary antibiotic resistant

bacterial strains. Although having low toxicity against human cell lines and in vivo animal

models, thiopeptides have only been used in the agricultural industry due to their low

solubility in water. En route to the total synthesis of the thiopeptide lactocillin (119), a

platform for the synthesis of novel thiopeptides has been developed. The route allows for

rapid construction of the 29-membered macrocyclic core with synthetic handles for analog synthesis. Utilizing this route, derivative synthesis has begun with the intention of

ultimately discovering novel thiopeptides with improved pharmacokinetics.