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.