Design and Synthesis of 4-Hydroxy Proline Based Library for Pharmaceutical Uses

Trans-4-hydroxy proline is readily accessible, stereochemically rich molecule that offers multiple sites for functionality. This functionality can be used to attach different pharmacophores in an attempt to create a diverse library of compounds for further medical and biological research. The starting material is readily available and inexpensive which aids in quickly being able to build this library with very low cost for the researcher. Proline derivatives have been used in biologically active compounds both in nature and in synthetic chemistry. Trans-4-hydroxy proline has 3 distinct sites for functionalization. Previous work in this group has shown great success in developing functionality at the 2-position with the attachment of various oxazoline and oxazole rings, but this work will focus on developing diversity at the 4-position. Through a few relatively easy chemical steps, I was able to develop two different functional groups at this position. The primary route for both functional groups goes from the alcohol at the 4-position to an azide. At this point, the synthesis is able to go in two different directions. The azide can be reduced to an amine and then converted to a variety of amides. The azide can also be reacted with various terminal alkynes using click chemistry to produce triazole ring structures. These two new functional groups can be coupled with previous work at the 2-position to potentially develop new biologically active compounds to be used in drug design and discovery. The long-term goal of this research would be to create functionality at the 1-, 2-, and 4-positions and aid in new drug design.