Development of Scalable Synthesis for Selected Protease uPA Inhibitors

Abstract

α-Aminophosphonate UAMC-00050 is a lead compound for the treatment of Dry Eye Disease. The Doctoral thesis discusses the optimization of a multigram synthesis of UAMC-00050. Every step has been carefully studied to improve the yield, and design of experiment (DoE) was used in the last reaction. Yttrium triflate was discovered as an efficient green catalyst for the synthesis of a key intermediate through a one-pot three-component Birum–Oleksyszyn reaction. The overall yield was increased from 3 % in the medicinal chemistry route to 22 % in the process development route. The optimized protocol was applied, with the necessary changes for the preparation of the close analogues of UAMC-00050: UAMC-0004206 and UAMC-0004207.