Fig. 1. M2FTC physicochemical characterization.

(A) Synthesis of aryl amino phosphochloridate. N-Cbz-L-Phenylalanine was dissolved in DMF and CFM. Cooled on ice. HATU, docosanol, imidazole and Et₃N were added and reaction was stirred at RT for 48 h. Product was dissolved in CFM and MeOH. Palladium on carbon was added and cooled to 4 °C, Et₃SiH was added and stirred for 16 h. Product was dissolved in DCM at −78 °C, Phenyl dichlorophosphate was then added, followed by Et₃N/CFM addition, stirred at 48 h RT. (B) FTC was dissolved in THF at −78 °C, ^tBuMgCl was added and stirred at 48–90 h at RT. FTC was then reacted with product formed in previous step with a 61% yield (C) Solubility of FTC and M2FTC in 1-octanol and water was measured at 37°C. Data are expressed as mean ± SEM for n = 3 samples were evaluated. Statistical significance was measured using one way ANOVA at ****P < 0.0001. (D) Fourier transformed infra-red spectroscopic (FT-IR) analysis showed the presence of carbonyl and aromatic stretching vibrations in the region of 2900 – 3100 cm⁻¹ for FTC and M2FTC and phosphoramide (P-N-H) bending vibrations between 1600 – 1700 cm⁻¹ in M2FTC, confirming the presence of these functionalities. (E) XRD analysis of FTC and M2FTC supporting unique atomic arrangement in the compounds crystal lattice. F) Hydrolysis study in different species’ plasma demonstrated chemical stability of M2FTC over 90% in both normal and heat inactivated human plasma up to 24 h at 37 °C and gradual hydrolysis observed of up to 40% in mice and rats, dog, rabbit and in monkey plasma over 24 h.