EFFICIENT AND DIVERSIFIABLE SYNTHESES OF STREPTOMYCES COELICOLOR GAMMA-BUTYROLACTONES

Streptomyces bacteria use γ-butyrolactone (GBL) hormones to signal biosynthesis of natural products, many of which are useful as medicines, agricultural chemicals, and chemical tools. These GBL hormones have been the target of synthetic efforts for over a decade due to their promising potential to unlock novel natural products that can aid in the fight against cancer, fungal infections, bacterial infections, and more. However, previous syntheses of the Streptomyces coelicolor GBLs suffer from lengthy syntheses, low yields, low enantioselectivity or diastereoselectivity, or lack of diversifiability. The work described herein bypasses each of these issues. The synthesis is shorter than previous efforts, accessing the final molecules in six steps while also having high enantioselectivity, diastereoselectivity, and overall yield. In addition, work has begun to create derivatives of these natural GBLs using five-membered lactam and thiolactone cores, which could have greater stability than the traditional lactone GBL core.