Dry eye disease (DED) is a widespread illness, with a prevalence ranging from 8.7 to 30.1 % of the population. Due to a limited number of therapies present on the market, development of new drugs is highly desirable. α-Aminophosphonate UAMC-00050, is a perspective lead compound for the treatment of DED. However, upscale of medicinal chemistry route for its preparation met with several problems: poor yields for some of the steps, hazardous reagents, and suboptimal environmental footprint. This doctoral thesis discuss the optimization of a multigram synthesis of UAMC-00050. In the update synthetic route, environmental unfriendly solvents were excluded and hazardous reagents were replaced with safer alternatives, more efficient in terms of atom economy. Every step was carefully studied to improve the yield and design of experiment (DoE) was used to find the optimum conditions 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. To reduce the process mass intensity, flash chromatography purifications of intermediates were substituted with alternative techniques (extraction, crystallization, antisolvent precipitation). 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 (a backup compound for UAMC-00050) and UAMC-0004207 (a compound that will be tested as proof of concept for the activity of α-amino-4-chlorophenolphosphonates). Finally, a series of chiral carbamates were prepared to test a diastereoselective Birum-Oleksyszyn reaction promoted by yttrium triflate. Various new α-aminophosphonates were synthesized with dr up to 75:25.